Modulation of ionic selectivity of cardiac Na channels : single channel analysis of "slip mode conductance"

心脏Na通道离子选择性的调节:“滑模电导”的单通道分析

基本信息

  • 批准号:
    11670663
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

The possibility of Ca^<2+> permeation through cardiac Na channels ("slip mode conductance") was explorerd through the analysis of voltage dependent block of Na channels by Ca^<2+>. Ca^<2+> block of Na channels was evident in rat and guinea-pig ventricular myocytes during cell-attached single channel recording with physiological ionic environment (140mM-Na^+ and 1 to 10mM-Ca^<2+> in the pipette solution). Increasing external Ca^<2+> concentration ([Ca^<2+>]_0) in the pipette solution reduced the unitary current amplitude predominantly at negative potentials. With [Ca^<2+>]_0>1mM, unitary current amplitude did not increase at potentials negative to -40mV in spite of augmented driving forces. Application of 5μM-isoproterenol potentiated the single channel activity elicited by depolarizing pulses from the holding potential of-120mV, indicating that the channels in the patch under examination were modified by protein kinase A (PKA) stimulation. Increased activity was also confirmed with veratridine-modified Na channels, where channel openings were markedly prolonged. In either case, isoproterenol-induced potentiation did not reduce nor alter the properties of Ca^<2+> block of cardiac Na channels, as evidenced by the stable unitary current amplitudes at potential levels between -20 and -60mV.These results indicate that interactions among Na^+, Ca^<2+> and the channel molecule were not modified with respect to permeation properties. They therefore argue against "slip mode" concept of classical cardiac Na channel, if a general concept of ion permeation through "multi-ion pores" is applicable to determine the ionic selectivity of Na channels.
通过分析Ca^<2 +>对Na通道的电压依赖性阻滞,探讨了Ca ^<2 +>通过心脏Na通道的可能性(“滑移模式电导”)。在生理离子环境(移液管溶液中140 mM-Na ^+和1 - 10 mM-Ca ^2+)下,在细胞贴附单通道记录过程中,大鼠和豚鼠心室肌细胞的Na通道明显受到Ca^2+阻滞。增加移液管溶液中的外部Ca^<2+>浓度([Ca^<2+>]_0)主要在负电位下降低单位电流幅度。当[Ca^<2+>]_0> 1 mM时,尽管驱动力增大,但在负电位至-40mV时,单位电流幅值并不增加。应用5μ M异丙肾上腺素可增强由-120mV保持电位的去极化脉冲引起的单通道活动,表明所检查的膜片中的通道被蛋白激酶A(PKA)刺激修饰。增加的活动也证实了藜芦碱修饰的钠通道,通道开放显着延长。在这两种情况下,异丙肾上腺素诱导的增强作用既不降低也不改变Ca^<2+>对心脏Na通道的阻滞特性,这一点可以从电位水平在-20和-60 mV之间稳定的单一电流幅度得到证明。这些结果表明Na^+、Ca^<2+>和通道分子之间的相互作用在渗透特性方面没有改变。因此,如果离子通过“多离子孔”渗透的一般概念适用于确定钠通道的离子选择性,他们反对经典心脏钠通道的“滑动模式”概念。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoshinaga T.,Zhang S.,Niidome T.,Hiraoka M.,Hirano Y.: "Potentiation of recombinant L-type Ca channel currents by α 1-adrenoceptors coexpressed in baby hamster kidney (BHK) cells."Life Sciences. 64. 1643-1651 (1999)
Yoshinaga T.、Zhang S.、Niidome T.、Hiraoka M.、Hirano Y.:“在幼仓鼠肾 (BHK) 细胞中共表达的 α 1-肾上腺素受体对重组 L 型 Ca 通道电流的增强。”生命科学 64。 .1643-1651 (1999)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Hirano Y.,Yoshinaga T.,Murata M.,Hiraoka M.: "Prepulse-induced mode2 gating behavior with and without β-adrenergic stimulation in cardiac L-type Ca channels."American Journal of Physiology. 276(Cell Physiol.45). C1338-C1345 (1999)
Hirano Y.、Yoshinaga T.、Murata M.、Hiraoka M.:“在心脏 L 型 Ca 通道中,有或没有 β-肾上腺素刺激时,前脉冲诱导的 2 型门控行为。”美国生理学杂志 276(细胞生理学)。 ) )。 C1338-C1345 (1999)
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HIRANO Yuji其他文献

HIRANO Yuji的其他文献

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{{ truncateString('HIRANO Yuji', 18)}}的其他基金

Dual modulation of Ca channels by intracellular Ca^<2+> concentration
细胞内 Ca^2 浓度对 Ca 通道的双重调节
  • 批准号:
    03670443
  • 财政年份:
    1991
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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CAREER: Charge Delocalization: A New Tool for Controlling Ionic Selectivity and Conductivity of Ion-Exchange Membranes
职业:电荷离域:控制离子交换膜的离子选择性和电导率的新工具
  • 批准号:
    2237122
  • 财政年份:
    2023
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Continuing Grant
The molecular basis of ionic selectivity in nicotinic-type ion channel receptors
烟碱型离子通道受体离子选择性的分子基础
  • 批准号:
    DP130101702
  • 财政年份:
    2013
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Discovery Projects
Ionic Selectivity and Molecular Organization of Red Cell Membranes
红细胞膜的离子选择性和分子组织
  • 批准号:
    68B6714
  • 财政年份:
    1968
  • 资助金额:
    $ 2.24万
  • 项目类别:
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