Regional differences in the pacemaker activity of the heart

心脏起搏器活动的区域差异

• 批准号: 07044244
• 负责人: KODAMA Itsuo
• 金额: $ 2.3万
• 依托单位: Res.Inst.of Environ.Med., Nagoya Univ.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07044244/
• 关键词: sinoatrial node; spontaneous activity; action potential; ion channel; electrophysiology; heart; 自発活動電位; イオン電流; パッチクランプ; 4-aminopyridine; 細胞歩調取り機能; 電気生理学的多様性; 細胞内イオン動態

The SA node is an inhomogeneous structure in terms of structure, properties and function. We have investigated the possible regional deferences in the role of various membrane currents in the pacemaker activity in rabbit SA node preparations. Block of L type Ca^<2+> current (I_<Ca>) by 2muM nifedipine abolished spontaneous action potentials in the center, but not in the periphery, in the intact SA node and small ball-like specimens of the SA node. In contrast, block of Na^+ current (I_<Na>) by 20muM TTX had no effect on the electrical activity in small balls from the center, but it slowed the spontaneous acivity in balls from the periphery of the SA node. An application of 2 mM Cs^+,1muM UL-SF 49 or 3muM ZD7288, which has been reported to block hyperpolarization-activated current (I_f), decreased pacemaker slope and spontaneous rate of small balls of the SA node. The decrease was largest in balls from the periphery and least in balls from the center. These results suggest that I_<Ca> Plays an obligatory role in pacemaking in the center, whereas I_<Na> Plays a major role in pacemaking in the periphery, and that the contribution of I_f to spontaneous activity is greater in the periphery than in the center of the SA node. 4-aminopyridine (4-AP), which is known to block a population of K^+ current, caused a marked prolongation of action potential and a slowing of spontaneous rate in the periphery, but it accelerated spontaneous activity in the center of the SA node. This suggests that 4-AP-sensitive currents are also involved in the heterogeneity of the electrical activity within the SA node.

SA节点在结构、性质和功能上是一种非均匀结构。我们已经调查了可能的区域差异的作用，各种膜电流的起搏活动在兔SA结准备。用2 μ M硝苯地平阻断L型Ca^&lt;2+&gt;电流（I_<Ca>），可使完整的窦房结和窦房结小球样标本的中央自发动作电位消失，但外周的自发动作电位不消失。与此相反，用20 μ M TTX阻断Na^+电流（I_<Na>）对窦房结中心小球的电活动没有影响，但它减慢了窦房结外围小球的自发活动。应用2 mM Cs^+、1 μ M UL-SF 49或3 μ M ZD 7288，据报道可阻断超极化激活电流（I_f），降低起搏斜率和SA结小球的自发频率。减少最大的球从外围和最少的球从中心。这些结果表明，I_<Ca>f在窦房结中心区起着必不可少的作用，而<Na>在周边区起着主要的作用，并且在窦房结周边区I_f对自发活动的贡献大于窦房结中心区。4-已知氨基吡啶（4-AP）可阻断K^+电流群，它可引起动作电位显著延长，并使外周的自发频率减慢，但它可加速窦房结中心的自发活动。这表明4-AP敏感电流也参与SA结内电活动的异质性。

项目成果

Ei-ichi Watanabe: "Inactivation of calcium current is involved in overdrive suppression of rabbit sinoatrial node cells" American Journal of Physiology. 271. H2097-H2107 (1996)

Ei-ichi Watanabe：“钙电流失活与兔窦房结细胞的过度抑制有关”美国生理学杂志。

Muhammad Nikmaram: "The Na^+ current plays an important role inpacemaker activity in the periphery, but not in center, of the rabbit sinoatrial node" Journal of Physiology. 491P. 154 (1996)

Muhammad Nikmaram：“Na^电流在兔窦房结周围而非中心的起搏器活动中发挥重要作用”《生理学杂志》。

Muhammad R. Nikmaram: "The Na+ current plays an importent role in pacemaker activity in the periphery, but not the centre, of the rabbit sinoatrial node" Journal of Physiology. (in press). (1996)

Muhammad R. Nikmaram：“Na 电流在兔窦房结周围而非中心的起搏器活动中发挥着重要作用”《生理学杂志》。

Haruo Honjo: "Correlation between electrical activity and the size of rabbit sino-atrial node cells" Journal of Physiology. 496. 795-808 (1996)

Haruo Honjo：“电活动与兔窦房结细胞大小的相关性”生理学杂志。

Muhammad Nikmaram: "Variation in the effects of Cs^+,UL-SF 49 and ZD 7288 within the sino-atrial node" American Journal of Physiology. (in press). (1997)

Muhammad Nikmaram：“窦房结内 Cs^、UL-SF 49 和 ZD 7288 影响的变化”美国生理学杂志。