The Experts below are selected from a list of 141 Experts worldwide ranked by ideXlab platform

Hiroyasu Satoh - One of the best experts on this subject based on the ideXlab platform.

  • Role of T-type Ca2+ channel inhibitors in the pacemaker depolarization in rabbit sino-atrial nodal cells
    General Pharmacology-the Vascular System, 1995
    Co-Authors: Hiroyasu Satoh
    Abstract:

    Abstract 1. 1. Effects of T-type Ca2+ channel inhibitors, Ni2+ and tetramethrin, on the spontaneous action Potentials in rabbit sino-atrial nodal cells were examined. 2. 2. The firing rate of spontaneous activity was 201 ± 11 beats/min (n = 18). Experiments were performed at 36°C. 3. 3. Ni2+ (10−5 to 10−4 M) and tetramethrin (10−7 to 5 × 10−5M) caused a negative chronotropic effect. Both inhibitors did not affect the Maximum Diastolic Potential, and slowed the rate of depolarization during the diastole. 4. 4. In the presence of TTX (10−7 M), both inhibitors caused a stronger negative chronotropic effect, and hyperpolarized the Maximum Diastolic Potential. The Maximum rate of depolarization was enhanced, and the action Potential duration (at 50% repolarization) was prolonged. The action Potential amplitude was unaffected. Ni2+ had more potent actions than tetramethrin. 5. 5. T-type and other Ca2+ channel inhibitors affected only the late phase of pacemaker Potential, resulting in a negative chronotropic effect. 6. 6. These results indicate that T-type Ca2+ channel inhibitors (Ni2+ and tetramethrin) slow the pacemaker depolarization at the late phase (but not at the initial phase), resulting in a negative chronotropic effect in the sino-atrial nodal cells.

  • Electrophysiological Actions of Taurine on Spontaneously Beating Rabbit Sino-Atrial Nodal Cells
    Japanese Journal of Pharmacology, 1995
    Co-Authors: Hiroyasu Satoh
    Abstract:

    Effects of taurine on the spontaneous action Potentials in rabbit sino-atrial nodal cells were examined at different extracellular Ca2+ concentrations ([Ca]o). Experiments were performed at 36°C. The firing rate of spontaneous activity was 132.5± 12.1 beats/min (n= 18) in normal Tyrode''s solution ([Ca]o = 1.8 mM). Increasing [Ca]o level from 0.9 to 10.8 mM significantly changed the Maximum rate of depolarization. Other parameters of the action Potentials were unaffected. When [Ca]o was 0.9 mM, application of taurine (1 to 20 mM) tended to cause a positive chronotropic effect and hyperpolarized the Maximum Diastolic Potential. In the normal solution (at 1.8 mM [Ca]o), taurine significantly enhanced only the Maximum rate of depolarization. In contrast, under high [Ca]o (5.4 and 10.8 mM), taurine at 1 and 5 mM had a negative chronotropic effect, but 20 mM taurine had a positive chronotropic effect. Also, taurine shortened the action Potential duration and hyperpolarized the Maximum Diastolic Potential. The Maximum rate of depolarization was inhibited. In 10.8 mM [Ca]o solution, irregular spontaneous activity (dysrhythmias) occurred in 4 of 6 preparations, and addition of taurine (1 to 20 mM) abolished it. These results indicate that taurine modulates the action Potential configuration in the sino-atrial nodal cells dependent on [Ca]o.

  • Electrophysiological actions of adenosine and aminophylline in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1993
    Co-Authors: Hiroyasu Satoh
    Abstract:

    Effects of adenosine (30 to 200 μmol/l) on the spontaneous action Potentials and the membrane currents in rabbit sino-atrial node (SA) preparations were examined. Adenosine (30 μmol/l) lengthened the action Potential duration and the cycle length. At 100 μmol/l, adenosine also hyperpolarized the Maximum Diastolic Potential. However, the action Potential amplitude and the Maximum rate of depolarization $$\dot V$$ _max) were unaffected. In the presence of adenosine (200 μmol/l) addition of aminophylline (an antagonist) (23–46 μmol/l) shortened the cycle length and depolarized the Maximum Diastolic Potential to the contrary. Aminophylline did not antagonize the prolongation of the action Potential. Aminophylline (46 μmol/l) alone decreased the cycle length and the Maximum Diastolic Potential, but did not affect the action Potential amplitude, the action Potential duration and the $$\dot V$$ _max. In the presence of aminophylline (46 μmol/l). addition of adenosine (200 μmol/l) increased the cycle length and the action Potential duration, and decreased $$\dot V$$ _max. In voltage-clamp experiments, adenosine greatly shifted the background current in the outward direction. Holding Potential was −40 mV. Adenosine reduced a slow inward and a time-dependent outward current, in a concentration-dependent manner. Adenosine did not affect the time constant of inactivation phase and the voltages of the half-Maximum activation and inactivation for the slow inward current. The activation curve for the outward current was also unaffected. A hyperpolarization-activated inward current was decreased. In the presence of aminophylline (46 μmol/l), adenosine (200 μmol/l) decreased the slow inward current, the time-dependent outward current and the hyperpolarization-activated inward current. These results suggest that adenosine produces its actions on the heart by inhibition of ionic currents and activation of the outward background current.

  • Electrophysiological actions of adenosine and aminophylline in spontaneously beating and voltage-clamped rabbit sino-atrial node preparations
    Naunyn-Schmiedeberg's archives of pharmacology, 1993
    Co-Authors: Hiroyasu Satoh
    Abstract:

    Effects of adenosine (30 to 200 mumol/l) on the spontaneous action Potentials and the membrane currents in rabbit sino-atrial node (SA) preparations were examined. Adenosine (30 mumol/l) lengthened the action Potential duration and the cycle length. At 100 mumol/l, adenosine also hyperpolarized the Maximum Diastolic Potential. However, the action Potential amplitude and the Maximum rate of depolarization Vmax) were unaffected. In the presence of adenosine (200 mumol/l), addition of aminophylline (an antagonist) (23-46 mumol/l) shortened the cycle length and depolarized the Maximum Diastolic Potential to the contrary. Aminophylline did not antagonize the prolongation of the action Potential. Aminophylline (46 mumol/l) alone decreased the cycle length and the Maximum Diastolic Potential, but did not affect the action Potential amplitude, the action Potential duration and the Vmax. In the presence of aminophylline (46 mumol/l), addition of adenosine (200 mumol/l) increased the cycle length and the action Potential duration, and decreased Vmax. In voltage-clamp experiments, adenosine greatly shifted the background current in the outward direction. Holding Potential was -40 mV. Adenosine reduced a slow inward and a time-dependent outward current, in a concentration-dependent manner. Adenosine did not affect the time constant of inactivation phase and the voltages of the half-Maximum activation and inactivation for the slow inward current. The activation curve for the outward current was also unaffected. A hyperpolarization-activated inward current was decreased. In the presence of aminophylline (46 mumol/l), adenosine (200 mumol/l) decreased the slow inward current, the time-dependent outward current and the hyperpolarization-activated inward current.(ABSTRACT TRUNCATED AT 250 WORDS)

Takahiro Isono - One of the best experts on this subject based on the ideXlab platform.

  • Rapidly and slowly activating components of delayed rectifier K+ current in guinea‐pig sino‐atrial node pacemaker cells
    The Journal of Physiology, 2002
    Co-Authors: Hiroshi Matsuura, Tsuguhisa Ehara, Wei-guang Ding, Mariko Omatsu-kanbe, Takahiro Isono
    Abstract:

    The components and properties of the delayed rectifier K+ current (IK) in isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using the whole-cell configuration of the patch-clamp technique. An envelope of tails test was conducted by applying depolarizing pulses from a holding Potential of −50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of the tail current amplitude elicited upon return to the holding Potential to the magnitude of the time-dependent outward current activated during depolarizing steps was dependent on the pulse duration, while after exposure to the selective IKr inhibitor E-4031 (5 μm) this current ratio became practically constant irrespective of the pulse duration. These observations are consistent with the presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly activating components of IK (IKr and IKs, respectively) in guinea-pig SA node cells. The activation range for IKr, defined as the E-4031-sensitive current (half-maximal activation voltage (V1/2) of −26.2 mV) was much more negative than that for IKs, defined as the E-4031-resistant current (V1/2 of +17.2 mV). IKr exhibited a marked inward rectification at Potentials positive to −50 mV, whereas IKs showed only a slight rectification. In the current-clamp experiments, bath application of E-4031 (0.5 and 5 μm) initially slowed the repolarization at Potentials negative to approximately −30 mV and produced a significant depolarization of the Maximum Diastolic Potential, followed by the arrest of electrical activity, thus indicating that the late phase of the repolarization leading to the Maximum Diastolic Potential at around −60 mV in spontaneous action Potentials is primarily produced by IKr in guinea-pig SA node cells. External application of the selective IKs inhibitor 293B (30 μm) also delayed the repolarization process at Potentials negative to about −20 mV and induced moderate depolarization of the Maximum Diastolic Potential leading to the arrest of the spontaneous activity. These results provide evidence to suggest that both IKr and IKs are present and play crucial roles in the spontaneous electrical activity of guinea-pig SA node pacemaker cells.

  • Rapidly and slowly activating components of delayed rectifier K(+) current in guinea-pig sino-atrial node pacemaker cells.
    The Journal of physiology, 2002
    Co-Authors: Hiroshi Matsuura, Tsuguhisa Ehara, Wei-guang Ding, Mariko Omatsu-kanbe, Takahiro Isono
    Abstract:

    The components and properties of the delayed rectifier K(+) current (I(K)) in isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using the whole-cell configuration of the patch-clamp technique. An envelope of tails test was conducted by applying depolarizing pulses from a holding Potential of -50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of the tail current amplitude elicited upon return to the holding Potential to the magnitude of the time-dependent outward current activated during depolarizing steps was dependent on the pulse duration, while after exposure to the selective I(Kr) inhibitor E-4031 (5 microM) this current ratio became practically constant irrespective of the pulse duration. These observations are consistent with the presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly activating components of I(K) (I(Kr) and I(Ks), respectively) in guinea-pig SA node cells. The activation range for I(Kr), defined as the E-4031-sensitive current (half-maximal activation voltage (V(1/2)) of -26.2 mV) was much more negative than that for I(Ks), defined as the E-4031-resistant current (V(1/2) of +17.2 mV). I(Kr) exhibited a marked inward rectification at Potentials positive to -50 mV, whereas I(Ks) showed only a slight rectification. In the current-clamp experiments, bath application of E-4031 (0.5 and 5 microM) initially slowed the repolarization at Potentials negative to approximately -30 mV and produced a significant depolarization of the Maximum Diastolic Potential, followed by the arrest of electrical activity, thus indicating that the late phase of the repolarization leading to the Maximum Diastolic Potential at around -60 mV in spontaneous action Potentials is primarily produced by I(Kr) in guinea-pig SA node cells. External application of the selective I(Ks) inhibitor 293B (30 microM) also delayed the repolarization process at Potentials negative to about -20 mV and induced moderate depolarization of the Maximum Diastolic Potential leading to the arrest of the spontaneous activity. These results provide evidence to suggest that both I(Kr) and I(Ks) are present and play crucial roles in the spontaneous electrical activity of guinea-pig SA node pacemaker cells.

Hiroshi Matsuura - One of the best experts on this subject based on the ideXlab platform.

  • Rapidly and slowly activating components of delayed rectifier K+ current in guinea‐pig sino‐atrial node pacemaker cells
    The Journal of Physiology, 2002
    Co-Authors: Hiroshi Matsuura, Tsuguhisa Ehara, Wei-guang Ding, Mariko Omatsu-kanbe, Takahiro Isono
    Abstract:

    The components and properties of the delayed rectifier K+ current (IK) in isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using the whole-cell configuration of the patch-clamp technique. An envelope of tails test was conducted by applying depolarizing pulses from a holding Potential of −50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of the tail current amplitude elicited upon return to the holding Potential to the magnitude of the time-dependent outward current activated during depolarizing steps was dependent on the pulse duration, while after exposure to the selective IKr inhibitor E-4031 (5 μm) this current ratio became practically constant irrespective of the pulse duration. These observations are consistent with the presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly activating components of IK (IKr and IKs, respectively) in guinea-pig SA node cells. The activation range for IKr, defined as the E-4031-sensitive current (half-maximal activation voltage (V1/2) of −26.2 mV) was much more negative than that for IKs, defined as the E-4031-resistant current (V1/2 of +17.2 mV). IKr exhibited a marked inward rectification at Potentials positive to −50 mV, whereas IKs showed only a slight rectification. In the current-clamp experiments, bath application of E-4031 (0.5 and 5 μm) initially slowed the repolarization at Potentials negative to approximately −30 mV and produced a significant depolarization of the Maximum Diastolic Potential, followed by the arrest of electrical activity, thus indicating that the late phase of the repolarization leading to the Maximum Diastolic Potential at around −60 mV in spontaneous action Potentials is primarily produced by IKr in guinea-pig SA node cells. External application of the selective IKs inhibitor 293B (30 μm) also delayed the repolarization process at Potentials negative to about −20 mV and induced moderate depolarization of the Maximum Diastolic Potential leading to the arrest of the spontaneous activity. These results provide evidence to suggest that both IKr and IKs are present and play crucial roles in the spontaneous electrical activity of guinea-pig SA node pacemaker cells.

  • Rapidly and slowly activating components of delayed rectifier K(+) current in guinea-pig sino-atrial node pacemaker cells.
    The Journal of physiology, 2002
    Co-Authors: Hiroshi Matsuura, Tsuguhisa Ehara, Wei-guang Ding, Mariko Omatsu-kanbe, Takahiro Isono
    Abstract:

    The components and properties of the delayed rectifier K(+) current (I(K)) in isolated guinea-pig sino-atrial (SA) node pacemaker cells were investigated using the whole-cell configuration of the patch-clamp technique. An envelope of tails test was conducted by applying depolarizing pulses from a holding Potential of -50 mV to +30 mV for various durations ranging from 40 to 2000 ms. The ratio of the tail current amplitude elicited upon return to the holding Potential to the magnitude of the time-dependent outward current activated during depolarizing steps was dependent on the pulse duration, while after exposure to the selective I(Kr) inhibitor E-4031 (5 microM) this current ratio became practically constant irrespective of the pulse duration. These observations are consistent with the presence of the E-4031-sensitive, rapidly activating and E-4031-resistant, slowly activating components of I(K) (I(Kr) and I(Ks), respectively) in guinea-pig SA node cells. The activation range for I(Kr), defined as the E-4031-sensitive current (half-maximal activation voltage (V(1/2)) of -26.2 mV) was much more negative than that for I(Ks), defined as the E-4031-resistant current (V(1/2) of +17.2 mV). I(Kr) exhibited a marked inward rectification at Potentials positive to -50 mV, whereas I(Ks) showed only a slight rectification. In the current-clamp experiments, bath application of E-4031 (0.5 and 5 microM) initially slowed the repolarization at Potentials negative to approximately -30 mV and produced a significant depolarization of the Maximum Diastolic Potential, followed by the arrest of electrical activity, thus indicating that the late phase of the repolarization leading to the Maximum Diastolic Potential at around -60 mV in spontaneous action Potentials is primarily produced by I(Kr) in guinea-pig SA node cells. External application of the selective I(Ks) inhibitor 293B (30 microM) also delayed the repolarization process at Potentials negative to about -20 mV and induced moderate depolarization of the Maximum Diastolic Potential leading to the arrest of the spontaneous activity. These results provide evidence to suggest that both I(Kr) and I(Ks) are present and play crucial roles in the spontaneous electrical activity of guinea-pig SA node pacemaker cells.

Mayurika Desai - One of the best experts on this subject based on the ideXlab platform.

  • Maximum Diastolic Potential of human induced pluripotent stem cell derived cardiomyocytes depends critically on ikr
    PLOS ONE, 2012
    Co-Authors: Michael Xavier Doss, Jose M Di Diego, Robert J Goodrow, Jonathan M Cordeiro, Vladislav V Nesterenko, Hector Barajasmartinez, Janire Urrutia, Mayurika Desai, Jacqueline A Treat, Agapios Sachinidis
    Abstract:

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action Potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl2 (n = 22). Patch-clamp techniques were used to record IKr and IK1 from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p<0.001) and generated early afterdepolarizations in 8/21 preparations. In 13/21 BC, E-4031 rapidly depolarized the clusters leading to inexcitability. BaCl2, at concentrations that selectively block IK1 (50–100 µM), failed to depolarize the majority of clusters (13/22). Patch-clamp experiments revealed very low or negligible IK1 in 53% (20/38) of the cells studied, but presence of IKr in all (11/11). Consistent with the electrophysiological data, RT-PCR and immunohistochemistry studies showed relatively poor mRNA and protein expression of IK1 in the majority of cells, but robust expression of IKr. In contrast to recently reported studies, our data point to major deficiencies of hiPSC-CM, with remarkable diversity of electrophysiologic phenotypes as well as pharmacologic responsiveness among beating clusters and cells up to 121 days post-differentiation (dpd). The vast majority have a Maximum Diastolic Potential that depends critically on IKr due to the absence of IK1. Thus, efforts should be directed at producing more specialized and mature hiPSC-CM for future therapeutic applications.

  • Maximum Diastolic Potential of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Depends Critically on IKr
    PLOS ONE, 2012
    Co-Authors: Michael Xavier Doss, Jose M Di Diego, Robert J Goodrow, Jonathan M Cordeiro, Vladislav V Nesterenko, Janire Urrutia, Hector Barajas-martinez, Mayurika Desai
    Abstract:

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action Potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl2 (n = 22). Patch-clamp techniques were used to record IKr and IK1 from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p

Robert J Goodrow - One of the best experts on this subject based on the ideXlab platform.

  • Triggered Ca2+ Waves Induce Depolarization of Maximum Diastolic Potential and Action Potential Prolongation in Dog Atrial Myocytes
    Circulation-arrhythmia and Electrophysiology, 2020
    Co-Authors: Georg Gussak, Robert J Goodrow, Jonathan M Cordeiro, William Marszalec, Shin Yoo, Rishi Modi, Caitlin O’callaghan, Gary L. Aistrup, Giedrius Kanaporis, Lothar A. Blatter
    Abstract:

    Background: We have identified a novel form of abnormal Ca2+ wave activity in normal and failing dog atrial myocytes which occurs during the action Potential (AP) and is absent during diastole. The...

  • Maximum Diastolic Potential of human induced pluripotent stem cell derived cardiomyocytes depends critically on ikr
    PLOS ONE, 2012
    Co-Authors: Michael Xavier Doss, Jose M Di Diego, Robert J Goodrow, Jonathan M Cordeiro, Vladislav V Nesterenko, Hector Barajasmartinez, Janire Urrutia, Mayurika Desai, Jacqueline A Treat, Agapios Sachinidis
    Abstract:

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action Potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl2 (n = 22). Patch-clamp techniques were used to record IKr and IK1 from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p<0.001) and generated early afterdepolarizations in 8/21 preparations. In 13/21 BC, E-4031 rapidly depolarized the clusters leading to inexcitability. BaCl2, at concentrations that selectively block IK1 (50–100 µM), failed to depolarize the majority of clusters (13/22). Patch-clamp experiments revealed very low or negligible IK1 in 53% (20/38) of the cells studied, but presence of IKr in all (11/11). Consistent with the electrophysiological data, RT-PCR and immunohistochemistry studies showed relatively poor mRNA and protein expression of IK1 in the majority of cells, but robust expression of IKr. In contrast to recently reported studies, our data point to major deficiencies of hiPSC-CM, with remarkable diversity of electrophysiologic phenotypes as well as pharmacologic responsiveness among beating clusters and cells up to 121 days post-differentiation (dpd). The vast majority have a Maximum Diastolic Potential that depends critically on IKr due to the absence of IK1. Thus, efforts should be directed at producing more specialized and mature hiPSC-CM for future therapeutic applications.

  • Maximum Diastolic Potential of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Depends Critically on IKr
    PLOS ONE, 2012
    Co-Authors: Michael Xavier Doss, Jose M Di Diego, Robert J Goodrow, Jonathan M Cordeiro, Vladislav V Nesterenko, Janire Urrutia, Hector Barajas-martinez, Mayurika Desai
    Abstract:

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) hold promise for therapeutic applications. To serve these functions, the hiPSC-CM must recapitulate the electrophysiologic properties of native adult cardiomyocytes. This study examines the electrophysiologic characteristics of hiPSC-CM between 11 and 121 days of maturity. Embryoid bodies (EBs) were generated from hiPS cell line reprogrammed with Oct4, Nanog, Lin28 and Sox2. Sharp microelectrodes were used to record action Potentials (AP) from spontaneously beating clusters (BC) micro-dissected from the EBs (n = 103; 37°C) and to examine the response to 5 µM E-4031 (n = 21) or BaCl2 (n = 22). Patch-clamp techniques were used to record IKr and IK1 from cells enzymatically dissociated from BC (n = 49; 36°C). Spontaneous cycle length (CL) and AP characteristics varied widely among the 103 preparations. E-4031 (5 µM; n = 21) increased Bazett-corrected AP duration from 291.8±81.2 to 426.4±120.2 msec (p