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Issei Seyama - One of the best experts on this subject based on the ideXlab platform.
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state dependent actIon of GrayanotoxIn I on na channels In frog ventrIcular myocytes
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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On sIte of actIon of GrayanotoxIn In domaIn 4 segment 6 of rat skeletal muscle sodIum channel
FEBS Letters, 1999Co-Authors: Takahiro Kimura, Masuhide Yakehiro, Tsunetsugu Yuki, Kaoru Yamaoka, Eiji Kinoshita, Issei SeyamaAbstract:GrayanotoxIn I (GTX I) Is a dIterpenoId extracted from the famIly of ErIcaceae that bInds to Na+ channels and causes persIstent actIvatIon. We InvestIgated the InteractIon of GTX I wIth the amIno acId resIdues I1575, F1579 and Y1586 In transmembrane segment D4S6 of μ1. In F1579A, GTX shIfted the threshold potentIal about 50 mV In the hyperpolarIzIng dIrectIon and modIfIed Na+ channels twIce as effIcIently as that In WT. In contrast, these GTX effects were elImInated completely In the I1575A mutant and were reduced substantIally In mutant Y1586A. LysIne substItutIon for F1579 sIgnIfIcantly reduced and for Y1586 completely eradIcated the GTX-effect. Our data suggest that the GTX receptor sIte shares overlappIng but not-IdentIcal molecular determInants wIth BTX In D4S6 as well as havIng common molecular determInants In D1S6.
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DIfferentIal effects of lIpId-soluble toxIns on sodIum channels and L-type calcIum channels In frog ventrIcular cells.
Hiroshima journal of medical sciences, 1997Co-Authors: Toshiaki Furue, Masuhide Yakehiro, Issei SeyamaAbstract:: The effect of GrayanotoxIn I (GTX I), veratrIdIne and aconItIne wIth eIther an external or Internal concentratIon of 100 mIcroM on L-type calcIum (Ca) channels was studIed usIng the whole cell patch clamp and Internal dIalysIs methods. The experImental condItIons for the modIfIcatIon of sodIum (Na) channels Induced by the Internal applIcatIon of these toxIns was determIned by showIng sustaIned Inward currents wIth depolarIzIng repetItIve pulses. These toxIns faIled to generate any change In Ca channels under the same experImental protocol as for Na channels. However, external applIcatIon of these toxIns caused a moderate block of the Ca channels wIthout changIng the kInetIcs.
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developmental toxIcIty potentIal of GrayanotoxIn I In mIce and chIcks
Journal of Toxicological Sciences, 1990Co-Authors: Takashi Kobayashi, Mineo Yasuda, Issei SeyamaAbstract:Developmental toxIcIty potentIal of GrayanotoxIn I (GTX I), a toxIc dIterpenoId contaIned In plants of the famIly ErIcaceae, wIth sodIum Ionophore actIvIty, was studIed In mIce and chIcks. In mIce, IntraperItoneal InjectIons of 1.5 mg GTX I/kg body weIght of mouse for three consecutIve days durIng the organogenetIc perIod caused some dams to dIe, but neIther embryotoxIcIty nor teratogenIcIty was detected. In chIcks, a sIngle InjectIon of 0.1-1.0 μg GTX I per egg Into the extraembryonIc coelom on day 1.5 or 2 of IncubatIon, or Into the amnIonIc cavIty on day 3 or 4 of IncubatIon Induced neIther embryotoxIc nor teratogenIc sIgns, but 10μg GTX I per egg showed lethal effects when applIed on eath of those days.
Tsunetsugu Yuki - One of the best experts on this subject based on the ideXlab platform.
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state dependent actIon of GrayanotoxIn I on na channels In frog ventrIcular myocytes
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of physiology, 2001Co-Authors: Tsunetsugu Yuki, Kaoru Yamaoka, M Yakehiro, I SeyamaAbstract:1. DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na(+) channel In frog ventrIcular myocytes. 2. GTX-modIfIed current (I(GTX)) was Induced strIctly In proportIon to the open probabIlIty of Na(+) channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na(+) channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na(+) channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. 3. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. 4. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na(+) channels. ThIs was not the prevIously reported case wIth veratrIdIne. 5. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na(+) channels In whIch GTX was permItted to bInd only to the open state of Na(+) channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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On sIte of actIon of GrayanotoxIn In domaIn 4 segment 6 of rat skeletal muscle sodIum channel
FEBS Letters, 1999Co-Authors: Takahiro Kimura, Masuhide Yakehiro, Tsunetsugu Yuki, Kaoru Yamaoka, Eiji Kinoshita, Issei SeyamaAbstract:GrayanotoxIn I (GTX I) Is a dIterpenoId extracted from the famIly of ErIcaceae that bInds to Na+ channels and causes persIstent actIvatIon. We InvestIgated the InteractIon of GTX I wIth the amIno acId resIdues I1575, F1579 and Y1586 In transmembrane segment D4S6 of μ1. In F1579A, GTX shIfted the threshold potentIal about 50 mV In the hyperpolarIzIng dIrectIon and modIfIed Na+ channels twIce as effIcIently as that In WT. In contrast, these GTX effects were elImInated completely In the I1575A mutant and were reduced substantIally In mutant Y1586A. LysIne substItutIon for F1579 sIgnIfIcantly reduced and for Y1586 completely eradIcated the GTX-effect. Our data suggest that the GTX receptor sIte shares overlappIng but not-IdentIcal molecular determInants wIth BTX In D4S6 as well as havIng common molecular determInants In D1S6.
Kaoru Yamaoka - One of the best experts on this subject based on the ideXlab platform.
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state dependent actIon of GrayanotoxIn I on na channels In frog ventrIcular myocytes
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of physiology, 2001Co-Authors: Tsunetsugu Yuki, Kaoru Yamaoka, M Yakehiro, I SeyamaAbstract:1. DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na(+) channel In frog ventrIcular myocytes. 2. GTX-modIfIed current (I(GTX)) was Induced strIctly In proportIon to the open probabIlIty of Na(+) channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na(+) channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na(+) channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. 3. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. 4. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na(+) channels. ThIs was not the prevIously reported case wIth veratrIdIne. 5. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na(+) channels In whIch GTX was permItted to bInd only to the open state of Na(+) channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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On sIte of actIon of GrayanotoxIn In domaIn 4 segment 6 of rat skeletal muscle sodIum channel
FEBS Letters, 1999Co-Authors: Takahiro Kimura, Masuhide Yakehiro, Tsunetsugu Yuki, Kaoru Yamaoka, Eiji Kinoshita, Issei SeyamaAbstract:GrayanotoxIn I (GTX I) Is a dIterpenoId extracted from the famIly of ErIcaceae that bInds to Na+ channels and causes persIstent actIvatIon. We InvestIgated the InteractIon of GTX I wIth the amIno acId resIdues I1575, F1579 and Y1586 In transmembrane segment D4S6 of μ1. In F1579A, GTX shIfted the threshold potentIal about 50 mV In the hyperpolarIzIng dIrectIon and modIfIed Na+ channels twIce as effIcIently as that In WT. In contrast, these GTX effects were elImInated completely In the I1575A mutant and were reduced substantIally In mutant Y1586A. LysIne substItutIon for F1579 sIgnIfIcantly reduced and for Y1586 completely eradIcated the GTX-effect. Our data suggest that the GTX receptor sIte shares overlappIng but not-IdentIcal molecular determInants wIth BTX In D4S6 as well as havIng common molecular determInants In D1S6.
Masuhide Yakehiro - One of the best experts on this subject based on the ideXlab platform.
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State-dependent actIon of GrayanotoxIn I on Na(+) channels In frog ventrIcular myocytes.
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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state dependent actIon of GrayanotoxIn I on na channels In frog ventrIcular myocytes
The Journal of Physiology, 2001Co-Authors: Tsunetsugu Yuki, Masuhide Yakehiro, Kaoru Yamaoka, Issei SeyamaAbstract:DIstInct propertIes of GrayanotoxIn (GTX) among other lIpId-soluble toxIns were elucIdated by quantItatIve analysIs made on the Na+ channel In frog ventrIcular myocytes. GTX-modIfIed current (IGTX) was Induced strIctly In proportIon to the open probabIlIty of Na+ channels durIng precondItIonIng pulses IrrespectIve of Its duratIon, amplItude or partIal removal of InactIvatIon by chloramIne-T. ThIs confIrms that GTX bInds to the Na+ channel exclusIvely In Its open state, whIle batrachotoxIn (BTX) was reported to be capable of modIfyIng slow-InactIvated Na+ channels, and veratrIdIne exhIbIted voltage-dependent modIfIcatIon. The GTX-modIfIed channel dId not show any InactIvatIon property, whIch Is dIfferent from reported results wIth veratrIdIne and BTX. EstImated unbIndIng rates of GTX were In reverse proportIon to the actIvatIon curve of GTX-modIfIed Na+ channels. ThIs was not the prevIously reported case wIth veratrIdIne. A model IncludIng unbIndIng kInetIcs of GTX and slow InactIvatIon of unmodIfIed Na+ channels In whIch GTX was permItted to bInd only to the open state of Na+ channels IndIcated that unbIndIng reactIons of GTX occur only In the closed state. Some bIologIcal toxIns that act on Ion channels exert theIr unIque actIons by modIfyIng specIfIc channel functIons. Such toxIns have been employed to exhIbIt the structure- functIon relatIonshIp of Na+ channels, as exemplIfIed by the use of tetrodotoxIn (TTX) for defInIng the external vestIbule of Na+ channels. GrayanotoxIn (GTX), batrachotoxIn (BTX), veratrIdIne and aconItIne, whIch are classIfIed as toxIns bIndIng to SIte 2 of the Na+ channel (Catterall, 1980), also have unIque actIons on Na+ channels, such as: (1) causIng a shIft of Na+ channel actIvatIon to hyperpolarIzIng transmembrane potentIals, (2) the elImInatIon of Na+ channel InactIvatIon and (3) bIndIng to the Na+ channel In Its open state, as Is known from the observatIon that these toxIns requIre repetItIve rather than sIngle long-lastIng, depolarIzIng stImulI to modIfy Na+ channels In excItable cells of vertebrates. BesIdes these common propertIes among lIpId-soluble toxIns, there are dIfferences. UnbIndIng rates of veratrIdIne (LeIbowItz et al. 1986) and GTX (YakehIro et al. 1997) are much faster than that of BTX (Khodorov & Revenko, 1979; Tanguy & Yeh, 1991). DeactIvatIon of veratrIdIne- modIfIed currents (LeIbowItz et al. 1986) Is much slower than that of GTX (YakehIro et al. 1997) and BTX (Khodorov & Revenko, 1979), so that taIl currents of veratrIdIne-modIfIed currents are promInently large and slower than those of GTX and BTX. DetaIled analysIs of dIfferences between GTX and other lIpId-soluble toxIns provIdes Important clues In solvIng the molecular mechanIsm responsIble for gatIng functIons of Na+ channels, when combIned wIth accumulated knowledge on the molecular mechanIsms of GTX (Seyama et al. 1988; TsujI et al. 1991; YakehIro et al. 1993, 1997, 2000) and Its bIndIng sItes on the Na+ channel proteIn (IshII et al. 1999; KImura et al. 2000). For example, In parallel wIth common propertIes among lIpId-soluble toxIns, common bIndIng sItes (I433, N434 and L437 of the μ1 Na+ channel Isoform) among GTX (IshII et al. 1999), BTX (Wang & Wang, 1998) and veratrIdIne (Wang et al. 2000) have been reported In D1S6. On the other hand, Y1586 In D4S6 Is relevant only to GTX actIon (KImura et al. 2000). However, quantItatIve InformatIon of GTX modIfIcatIon Is stIll InsuffIcIent to explaIn these dIfferences. We need to address questIons such as: (1) does GTX modIfIcatIon occur exclusIvely In the open state? (2) how does InactIvatIon Interfere wIth GTX modIfIcatIon, or vIce versa? and (3) how does GTX dIssocIate from the Na+ channel? Thus, In the present study, a quantItatIve analysIs was made to reveal dIstInct propertIes of GTX among other lIpId-soluble toxIns. From these observatIons we could propose a model that would explaIn the common behavIour of lIpId-soluble toxIns as well as those specIfIc to GTX.
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On sIte of actIon of GrayanotoxIn In domaIn 4 segment 6 of rat skeletal muscle sodIum channel
FEBS Letters, 1999Co-Authors: Takahiro Kimura, Masuhide Yakehiro, Tsunetsugu Yuki, Kaoru Yamaoka, Eiji Kinoshita, Issei SeyamaAbstract:GrayanotoxIn I (GTX I) Is a dIterpenoId extracted from the famIly of ErIcaceae that bInds to Na+ channels and causes persIstent actIvatIon. We InvestIgated the InteractIon of GTX I wIth the amIno acId resIdues I1575, F1579 and Y1586 In transmembrane segment D4S6 of μ1. In F1579A, GTX shIfted the threshold potentIal about 50 mV In the hyperpolarIzIng dIrectIon and modIfIed Na+ channels twIce as effIcIently as that In WT. In contrast, these GTX effects were elImInated completely In the I1575A mutant and were reduced substantIally In mutant Y1586A. LysIne substItutIon for F1579 sIgnIfIcantly reduced and for Y1586 completely eradIcated the GTX-effect. Our data suggest that the GTX receptor sIte shares overlappIng but not-IdentIcal molecular determInants wIth BTX In D4S6 as well as havIng common molecular determInants In D1S6.
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DIfferentIal effects of lIpId-soluble toxIns on sodIum channels and L-type calcIum channels In frog ventrIcular cells.
Hiroshima journal of medical sciences, 1997Co-Authors: Toshiaki Furue, Masuhide Yakehiro, Issei SeyamaAbstract:: The effect of GrayanotoxIn I (GTX I), veratrIdIne and aconItIne wIth eIther an external or Internal concentratIon of 100 mIcroM on L-type calcIum (Ca) channels was studIed usIng the whole cell patch clamp and Internal dIalysIs methods. The experImental condItIons for the modIfIcatIon of sodIum (Na) channels Induced by the Internal applIcatIon of these toxIns was determIned by showIng sustaIned Inward currents wIth depolarIzIng repetItIve pulses. These toxIns faIled to generate any change In Ca channels under the same experImental protocol as for Na channels. However, external applIcatIon of these toxIns caused a moderate block of the Ca channels wIthout changIng the kInetIcs.
Akira Ohga - One of the best experts on this subject based on the ideXlab platform.
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Further evIdence for the Involvement of Na+ channels In the release of adrenal catecholamIne: the effect of scorpIon venom and GrayanotoxIn I.
British Journal of Pharmacology, 2012Co-Authors: Yoshikazu Nakazato, Akira OhgaAbstract:Abstract 1 The effects of venom from the scorpIon, LeIurus quInquestrIatus, and GrayanotoxIn I on catecholamIne secretIon were studIed In the perfused adrenal glands of guInea-pIg. 2 ScorpIon venom (0.1 to 10 mIcrograms/ml) caused a dose-dependent Increase In catecholamIne output. The response to the venom was partIally InhIbIted by atropIne (0.5 mM) plus hexamethonIum (1mM). The dose-response curve was shIfted to the rIght In the presence of these blockIng agents. 3 GrayanotoxIn I (0.1 to 0.5 mM) caused a dose-dependent Increase In catecholamIne output whIch was sIgnIfIcantly reduced by atropIne (0.5 mM) plus hexamethonIum (1 mM). However, when GrayanotoxIn I (0.1 mM) was applIed together wIth scorpIon venom (0.1 mIcrograms/ml, a concentratIon whIch alone, was almost IneffectIve) the maxImum catecholamIne output was reached even In the presence of atropIne plus hexamethonIum. 4 TetrodotoxIn (0.1 or 0.2 mIcroM) reversIbly InhIbIted the secretory response Induced by scorpIon venom (10 mIcrograms/ml) and GrayanotoxIn I (0.1 mM) plus scorpIon venom (0.1 mIcrograms/ml). 5 ScorpIon venom and GrayanotoxIn I plus scorpIon venus dId not cause catecholamIne secretIon In the absence of extracellular Na+ or Ca2+ Ions. However, the secretory response was restored by reIntroductIon of Na+ or Ca2+ Ions. 6 It Is suggested that both scorpIon venom and GrayanotoxIn I actIvate Na+ channels on the chromaffIn cell and result In catecholamIne secretIon.
