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Eugene V Grishin - One of the best experts on this subject based on the ideXlab platform.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B 1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(β-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl 2 and KC1 solutions via ionic channels produced by latrotoxins (a-latrotoxin (a-LT) and α-latroinsectotoxin (a-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl 2 inhibited transmembrane current by 31.6±3% and by 61.8±3% from the trans-side of BLM for α-LT channels. Application of DMHT in the solution of 10 mM CaCl 2 to the cis-side of BLM decreased the current through the α-LIT and RTX channels by 52±4% and 50±5%, respectively. Addition of Cd 2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca 2+ -current across the α-LT channels caused its further decrease by 85 ±5% that coincides favorably with the intensity of Cd 2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on α-LT channels without considerable influence on the ionogenic groups of Ca 2+ -selective site inside the channel cavity. The binding kinetics of DMHT with the α-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of α-LT channel on either side of the BLM. The comparative analysis of effective radii measured for α-LT, α-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for α-LT channel on the trans-side (0.28±0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen. © 2006 Elsevier B.V. All rights reserved.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl2 and KCl solutions via ionic channels produced by latrotoxins (alpha-latrotoxin (alpha-LT) and alpha-latroinsectotoxin (alpha-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl2 inhibited transmembrane current by 31.6+/-3% and by 61.8+/-3% from the trans-side of BLM for alpha-LT channels. Application of DMHT in the solution of 10 mM CaCl2 to the cis-side of BLM decreased the current through the alpha-LIT and RTX channels by 52+/-4% and 50+/-5%, respectively. Addition of Cd2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca2+-current across the alpha-LT channels caused its further decrease by 85+/-5% that coincides favorably with the intensity of Cd2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on alpha-LT channels without considerable influence on the ionogenic groups of Ca2+-selective site inside the channel cavity. The binding kinetics of DMHT with the alpha-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of alpha-LT channel on either side of the BLM. The comparative analysis of effective radii measured for alpha-LT, alpha-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for alpha-LT channel on the trans-side (0.28+/-0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen.

Oleg Ya Shatursky - One of the best experts on this subject based on the ideXlab platform.

  • long open amphotericin channels revealed in cholesterol containing phospholipid membranes are blocked by Thiazole Derivative
    The Journal of Membrane Biology, 2014
    Co-Authors: Oleg Ya Shatursky, Olexander V Romanenko, N H Himmelreich
    Abstract:

    The action of antifungal drug, amphotericin B (AmB), on solvent-containing planar lipid bilayers made of sterols (cholesterol, ergosterol) and synthetic C14–C18 tail phospholipids (PCs) or egg PC has been investigated in a voltage-clamp mode. Within the range of PCs tested, a similar increase was achieved in the lifetime of one-sided AmB channels in cholesterol- and ergosterol-containing membranes with the C16 tail PC, DPhPC at sterol/DPhPC molar ratio ≤1. The AmB channel lifetimes decreased only at sterol/DPhPC molar ratio >1 that occurred with sterol/PC molar ratio of target cell membranes at a pathological state. These data obtained on bilayer membranes two times thicker than one-sided AmB channel length are consistent with the accepted AmB pore-forming mechanism, which is associated with membrane thinning around AmB–sterol complex in the lipid rafts. Our results show that AmB can create cytotoxic (long open) channels in cholesterol membrane with C14–C16 tail PCs and nontoxic (short open) channels with C17–C18 tail PCs as the lifetime of one-sided AmB channel depends on ~2–5 A difference in the thickness of sterol-containing C16 and C18 tail PC membranes. The reduction in toxic AmB channels efficacy can be required at the drug administration because C16 tails in native membrane PCs occur almost as often as C18 tails. The comparative analysis of AmB channel blocking by tetraethylammonium chloride, tetramethylammonium chloride and Thiazole Derivative of vitamin B1, 3-decyloxycarbonylmethyl-4-methyl-5-(2-hydroxyethyl) Thiazole chloride (DMHT), has proved that DMHT is a comparable substitute for both tetraalkylammonia that exhibits a much higher affinity.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B 1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(β-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl 2 and KC1 solutions via ionic channels produced by latrotoxins (a-latrotoxin (a-LT) and α-latroinsectotoxin (a-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl 2 inhibited transmembrane current by 31.6±3% and by 61.8±3% from the trans-side of BLM for α-LT channels. Application of DMHT in the solution of 10 mM CaCl 2 to the cis-side of BLM decreased the current through the α-LIT and RTX channels by 52±4% and 50±5%, respectively. Addition of Cd 2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca 2+ -current across the α-LT channels caused its further decrease by 85 ±5% that coincides favorably with the intensity of Cd 2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on α-LT channels without considerable influence on the ionogenic groups of Ca 2+ -selective site inside the channel cavity. The binding kinetics of DMHT with the α-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of α-LT channel on either side of the BLM. The comparative analysis of effective radii measured for α-LT, α-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for α-LT channel on the trans-side (0.28±0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen. © 2006 Elsevier B.V. All rights reserved.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl2 and KCl solutions via ionic channels produced by latrotoxins (alpha-latrotoxin (alpha-LT) and alpha-latroinsectotoxin (alpha-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl2 inhibited transmembrane current by 31.6+/-3% and by 61.8+/-3% from the trans-side of BLM for alpha-LT channels. Application of DMHT in the solution of 10 mM CaCl2 to the cis-side of BLM decreased the current through the alpha-LIT and RTX channels by 52+/-4% and 50+/-5%, respectively. Addition of Cd2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca2+-current across the alpha-LT channels caused its further decrease by 85+/-5% that coincides favorably with the intensity of Cd2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on alpha-LT channels without considerable influence on the ionogenic groups of Ca2+-selective site inside the channel cavity. The binding kinetics of DMHT with the alpha-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of alpha-LT channel on either side of the BLM. The comparative analysis of effective radii measured for alpha-LT, alpha-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for alpha-LT channel on the trans-side (0.28+/-0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen.

Yoshihiko Koga - One of the best experts on this subject based on the ideXlab platform.

  • Protective effects of D-penicillamine and a Thiazole Derivative, SM-8849, on pristane-induced arthritis in mice
    International Journal of Immunopharmacology, 1994
    Co-Authors: Fumio Nishikaku, Syunji Aono, Yoshihiko Koga
    Abstract:

    Abstract To evaluate the antiarthritic properties of a novel Thiazole Derivative, the drugs SM-8849, D -penicillamine and indomethacin were administered to pristane-injected DBA/1 mice. The mice were treated daily with the agents for 32 weeks, starting from the day of the pristane injection. Treatment with SM-8849 (50 mg/kg) resulted in an amelioration of arthritic disease, as assessed by clinical, radiographic, and histologic examinations. Similar results were obtained in mice treated with 50 mg/kg D -penicillamine, although this disease modifying antirheumatic drug was slightly less effective than the same dose of SM-8849. In contrast, indomethacin at the maximum tolerated dose of 2 mg/kg did not alter the course of the disease. SM-8849 and D -penicillamine were also shown to reduce serum levels of rheumatoid factors and the acute-phase reactant, serum amyloid P component. Indomethacin failed to affect either parameter. Flow cytometric analysis revealed an elevation in the T-cell population that expressed CD44, a marker of murine memory T-cells, in spleens from pristane-injected mice. SM-8849, but not D -penicillamine, prevented the increase in this cell population. These results led us to conclude that pristine-induced arthritis was a useful model for the evaluation of antirheumatic agents, in that using this model, we were able to distinguish disease modifying antirheumatic drugs from nonsteroidal anti-inflammatory drugs. Our findings also indicate that SM-8849 shows antiarthritic activity, with a unique mechanism of action, differing from that of D -penicillamine.

  • Suppression of murine collagen-induced arthritis by treatment with a novel Thiazole Derivative, SM-8849
    Immunopharmacology, 1993
    Co-Authors: Fumio Nishikaku, Yoshihiko Koga
    Abstract:

    Abstract The antiarthritic activity of a novel Thiazole Derivative, SM-8849, was compared with that of indomethacin and D -penicillamine, in mice with collagen-induced arthritis. SM-8849 reduced the incidence and severity of disease in collagen-immunized mice, as assessed by clinical observation. This efficacy was also confirmed by radiographic and histologic studies. Indomethacin produced an apparent reduction of the clinical score, but had only a marginal effect on bone destruction. D -penicillamine did not produce any improvement. Unlike indomethacin and D -penicillamine, SM-8849 reduced the serum levels of anti-type II collagen antibodies. Flow cytometric analysis of spleen cells from arthritic mice revealed an increase in T cells expressing activation antigens (class II antigens) in comparison with normal mice. Treatment with SM-8849, but not indomethacin or D -penicillamine, prevented the increase in Ia-bearing T cells. The results suggest that an effect of SM-8849 on immunocompetent cells may be responsible for the antiarthritic activity of the compound, and this would distinguish its action from that of traditional antirheumatic drugs.

N H Himmelreich - One of the best experts on this subject based on the ideXlab platform.

  • long open amphotericin channels revealed in cholesterol containing phospholipid membranes are blocked by Thiazole Derivative
    The Journal of Membrane Biology, 2014
    Co-Authors: Oleg Ya Shatursky, Olexander V Romanenko, N H Himmelreich
    Abstract:

    The action of antifungal drug, amphotericin B (AmB), on solvent-containing planar lipid bilayers made of sterols (cholesterol, ergosterol) and synthetic C14–C18 tail phospholipids (PCs) or egg PC has been investigated in a voltage-clamp mode. Within the range of PCs tested, a similar increase was achieved in the lifetime of one-sided AmB channels in cholesterol- and ergosterol-containing membranes with the C16 tail PC, DPhPC at sterol/DPhPC molar ratio ≤1. The AmB channel lifetimes decreased only at sterol/DPhPC molar ratio >1 that occurred with sterol/PC molar ratio of target cell membranes at a pathological state. These data obtained on bilayer membranes two times thicker than one-sided AmB channel length are consistent with the accepted AmB pore-forming mechanism, which is associated with membrane thinning around AmB–sterol complex in the lipid rafts. Our results show that AmB can create cytotoxic (long open) channels in cholesterol membrane with C14–C16 tail PCs and nontoxic (short open) channels with C17–C18 tail PCs as the lifetime of one-sided AmB channel depends on ~2–5 A difference in the thickness of sterol-containing C16 and C18 tail PC membranes. The reduction in toxic AmB channels efficacy can be required at the drug administration because C16 tails in native membrane PCs occur almost as often as C18 tails. The comparative analysis of AmB channel blocking by tetraethylammonium chloride, tetramethylammonium chloride and Thiazole Derivative of vitamin B1, 3-decyloxycarbonylmethyl-4-methyl-5-(2-hydroxyethyl) Thiazole chloride (DMHT), has proved that DMHT is a comparable substitute for both tetraalkylammonia that exhibits a much higher affinity.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B 1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(β-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl 2 and KC1 solutions via ionic channels produced by latrotoxins (a-latrotoxin (a-LT) and α-latroinsectotoxin (a-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl 2 inhibited transmembrane current by 31.6±3% and by 61.8±3% from the trans-side of BLM for α-LT channels. Application of DMHT in the solution of 10 mM CaCl 2 to the cis-side of BLM decreased the current through the α-LIT and RTX channels by 52±4% and 50±5%, respectively. Addition of Cd 2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca 2+ -current across the α-LT channels caused its further decrease by 85 ±5% that coincides favorably with the intensity of Cd 2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on α-LT channels without considerable influence on the ionogenic groups of Ca 2+ -selective site inside the channel cavity. The binding kinetics of DMHT with the α-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of α-LT channel on either side of the BLM. The comparative analysis of effective radii measured for α-LT, α-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for α-LT channel on the trans-side (0.28±0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen. © 2006 Elsevier B.V. All rights reserved.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl2 and KCl solutions via ionic channels produced by latrotoxins (alpha-latrotoxin (alpha-LT) and alpha-latroinsectotoxin (alpha-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl2 inhibited transmembrane current by 31.6+/-3% and by 61.8+/-3% from the trans-side of BLM for alpha-LT channels. Application of DMHT in the solution of 10 mM CaCl2 to the cis-side of BLM decreased the current through the alpha-LIT and RTX channels by 52+/-4% and 50+/-5%, respectively. Addition of Cd2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca2+-current across the alpha-LT channels caused its further decrease by 85+/-5% that coincides favorably with the intensity of Cd2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on alpha-LT channels without considerable influence on the ionogenic groups of Ca2+-selective site inside the channel cavity. The binding kinetics of DMHT with the alpha-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of alpha-LT channel on either side of the BLM. The comparative analysis of effective radii measured for alpha-LT, alpha-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for alpha-LT channel on the trans-side (0.28+/-0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen.

Olexander V Romanenko - One of the best experts on this subject based on the ideXlab platform.

  • long open amphotericin channels revealed in cholesterol containing phospholipid membranes are blocked by Thiazole Derivative
    The Journal of Membrane Biology, 2014
    Co-Authors: Oleg Ya Shatursky, Olexander V Romanenko, N H Himmelreich
    Abstract:

    The action of antifungal drug, amphotericin B (AmB), on solvent-containing planar lipid bilayers made of sterols (cholesterol, ergosterol) and synthetic C14–C18 tail phospholipids (PCs) or egg PC has been investigated in a voltage-clamp mode. Within the range of PCs tested, a similar increase was achieved in the lifetime of one-sided AmB channels in cholesterol- and ergosterol-containing membranes with the C16 tail PC, DPhPC at sterol/DPhPC molar ratio ≤1. The AmB channel lifetimes decreased only at sterol/DPhPC molar ratio >1 that occurred with sterol/PC molar ratio of target cell membranes at a pathological state. These data obtained on bilayer membranes two times thicker than one-sided AmB channel length are consistent with the accepted AmB pore-forming mechanism, which is associated with membrane thinning around AmB–sterol complex in the lipid rafts. Our results show that AmB can create cytotoxic (long open) channels in cholesterol membrane with C14–C16 tail PCs and nontoxic (short open) channels with C17–C18 tail PCs as the lifetime of one-sided AmB channel depends on ~2–5 A difference in the thickness of sterol-containing C16 and C18 tail PC membranes. The reduction in toxic AmB channels efficacy can be required at the drug administration because C16 tails in native membrane PCs occur almost as often as C18 tails. The comparative analysis of AmB channel blocking by tetraethylammonium chloride, tetramethylammonium chloride and Thiazole Derivative of vitamin B1, 3-decyloxycarbonylmethyl-4-methyl-5-(2-hydroxyethyl) Thiazole chloride (DMHT), has proved that DMHT is a comparable substitute for both tetraalkylammonia that exhibits a much higher affinity.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B 1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(β-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl 2 and KC1 solutions via ionic channels produced by latrotoxins (a-latrotoxin (a-LT) and α-latroinsectotoxin (a-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl 2 inhibited transmembrane current by 31.6±3% and by 61.8±3% from the trans-side of BLM for α-LT channels. Application of DMHT in the solution of 10 mM CaCl 2 to the cis-side of BLM decreased the current through the α-LIT and RTX channels by 52±4% and 50±5%, respectively. Addition of Cd 2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca 2+ -current across the α-LT channels caused its further decrease by 85 ±5% that coincides favorably with the intensity of Cd 2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on α-LT channels without considerable influence on the ionogenic groups of Ca 2+ -selective site inside the channel cavity. The binding kinetics of DMHT with the α-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of α-LT channel on either side of the BLM. The comparative analysis of effective radii measured for α-LT, α-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for α-LT channel on the trans-side (0.28±0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen. © 2006 Elsevier B.V. All rights reserved.

  • vitamin b1 Thiazole Derivative reduces transmembrane current through ionic channels formed by toxins from black widow spider venom and sea anemone in planar phospholipid membranes
    Biochimica et Biophysica Acta, 2007
    Co-Authors: Oleg Ya Shatursky, Tatyana M Volkova, Olexander V Romanenko, N H Himmelreich, Eugene V Grishin
    Abstract:

    The vitamin B1 (thiamine) structural analogue 3-decyloxycarbonylmethyl-4-methyl-5-(beta-hydroxyethyl) Thiazole chloride (DMHT) (0.1 mM) reversibly reduced transmembrane currents in CaCl2 and KCl solutions via ionic channels produced by latrotoxins (alpha-latrotoxin (alpha-LT) and alpha-latroinsectotoxin (alpha-LIT)) from black widow spider venom and sea anemone toxin (RTX) in the bilayer lipid membranes (BLMs). Introduction of DMHT from the cis-side of BLM bathed in 10 mM CaCl2 inhibited transmembrane current by 31.6+/-3% and by 61.8+/-3% from the trans-side of BLM for alpha-LT channels. Application of DMHT in the solution of 10 mM CaCl2 to the cis-side of BLM decreased the current through the alpha-LIT and RTX channels by 52+/-4% and 50+/-5%, respectively. Addition of Cd2+ (1 mM) to the cis- or trans-side of the membrane after the DMHT-induced depression of Ca2+-current across the alpha-LT channels caused its further decrease by 85+/-5% that coincides favorably with the intensity of Cd2+ blocking in control experiments without DMHT. These data suggest that DMHT inhibiting is not specific for latrotoxin channels only and DMHT may exert its action on alpha-LT channels without considerable influence on the ionogenic groups of Ca2+-selective site inside the channel cavity. The binding kinetics of DMHT with the alpha-LT channel shows no cooperativity and allows to expect that the DMHT binding site of the toxin is formed by one ionogenic group as the slopes of inhibition rate determined in log-log coordinates are 1.25 on the trans-side and 0.68 on the cis-side. Similar pK of binding (5.4 on the trans-side and 5.7 on the cis-side) also suggest that DMHT may interact with the same high affinity site of alpha-LT channel on either side of the BLM. The comparative analysis of effective radii measured for alpha-LT, alpha-LIT and RTX channels on the cis-side (0.9 nm, 0.53 nm and 0.55 nm, correspondingly) and for alpha-LT channel on the trans-side (0.28+/-0.18 nm) with the intensity of DMHT inhibitory action obtained on these channels allowed to conclude that the potency of DMHT inhibition increased on toxin pores of smaller lumen.