Ionic mechanisms underlying overdrive suppression of sinoatrial node cells

窦房结细胞超速抑制的离子机制

• 批准号: 07670775
• 负责人: HONJO Haruo
• 金额: $ 1.28万
• 依托单位: Research Institute of Environmental Medicine, Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-07670775/
• 关键词: sinoatrial node; spontaneous activity; overdrive suppression; L-type calcium current; inactivation; electrophysiology; patch clamp; heart; 細胞自動能; イオンチャネル; 細胞内イオン動態

Spontaneous activity of sinoatrial (SA) node pacemaker cells are transiently suppressed when driven at a rapid rate, and this phenomenon is known as "overdrive suppression". Although several mechanisms have been proposed, much remains to be clarified. Recently Boyett et al.showed that in ventricular cells, an increase in the rate of stimulation led to an abrupt, followed by a slow, decrease in the L-type calcium current (I_<Ca>). The slow decrease in I_<Ca> was interpreted as an ultra-slow voltage-dependent inactivation of I_<ca>. In the present study, the contribution of inactivation of I_<Ca> to overdrive suppression was investigated in rabbit SA node cells by use of the whole-cell clamp technique. In the current-clamp mode, rapid stimulation (6.7Hz) was followed by a transient suppression of spontaneous activity. In the voltage-clamp mode, an increase in the rate of depolarization from 1 to 6.7 Hz from a holding potential (HP) of -40 mV resulted in an abrupt, followed by a progressive, decrease in I_<Ca>. With a HP of -80 mV,an increase in the pulse rate caused much less reduction of I_<Ca>. When spontaneous action potential was interrupted by a train of high-frequency pulses (6.7 Hz) from a HP of-40mV,there was again a marked decrease in I_<Ca> during the train, and after the train there was a transient suppression of spontaneous activity. In contrast, an interruption by high-frequency pulses from a HP of -80mV caused no decrease in I_<Ca>, and there was no suppression of spontaneous activity after the train. Neither delayd rectifier potassium current nor hyperpolarization-activated current was affected after a train of high-frequency pulses. These results suggest that overdrive suppression in the SA node is, in part at least, the result of a rate-and voltage-dependent inactivation of I_<Ca>.

当高速驱动时，窦房结起搏器细胞的自发活动被短暂抑制，这种现象被称为“过度驱动抑制”。虽然提出了若干机制，但仍有许多有待澄清。最近Boyett等人发现，在心室细胞中，刺激率的增加导致l型钙电流突然下降，随后缓慢下降（I_<Ca>）。I_<Ca>的缓慢下降被解释为I_<Ca>的超慢电压依赖性失活。本研究采用全细胞钳夹技术研究了I_<Ca>失活对兔窦房结细胞过度抑制的贡献。在电流箝位模式下，快速刺激（6.7Hz）之后是短暂的自发活动抑制。在电压箝位模式下，保持电位（HP）为-40 mV时，去极化速率从1增加到6.7 Hz，导致I_<Ca>突然下降，随后逐渐下降。当HP为- 80mv时，脉冲速率的增加对I_<Ca>的影响较小。当脉冲强度为- 40mv的高频脉冲（6.7 Hz）打断自发性动作电位时，I_<Ca>在脉冲过程中再次显著降低，脉冲结束后自发性活动出现短暂抑制。相比之下，HP为-80mV的高频脉冲中断没有导致I_<Ca>的降低，也没有抑制训练后的自发活动。经过一系列高频脉冲后，延迟整流钾电流和超极化激活电流均不受影响。这些结果表明，窦房结的过度抑制至少在一定程度上是I_<Ca>的速率和电压依赖性失活的结果。

项目成果

児玉 逸雄: "Overdrive suppressionのイオン機序" 心臓. (印刷中). (1997)

Ituo Kodama：“超速抑制的离子机制”Heart（出版中）。

Kodama I., Watanabe E., Honjo H., Toyama J.and Boyett M.R.: "Ionic mechanisms of overdrive suppression." Heart. (in press). (1997)

Kodama I.、Watanabe E.、Honjo H.、Toyama J. 和 Boyett M.R.：“超速抑制的离子机制”。

児玉 逸雄: "洞房結節におけるoverdrive suppressionのイオン機序:L型Ca電流の緩徐不活性化の寄与" Japanese Journal of Electrocardiology. 16. 317-323 (1996)

Ituo Kodama：“窦房结超速抑制的离子机制：L 型 Ca 电流缓慢失活的贡献”日本心电学杂志 16. 317-323 (1996)。

Ei-ichi Watanabe: "Contribution of slow inactivation of L-type calcium current to overdrive suppression in rabbit sinoatrail node cells" Japanese Circulation Journal. 59. 420- (1995)

Ei-ichi Watanabe：“L 型钙电流缓慢失活对兔子窦房结细胞过度抑制的贡献”日本循环杂志。

Haruo Honjo: "Ultra-slow inactivation of L-type calcium current is responsible for overdrive suppression in the sinoatrial node" The 11th Asian-Pacific Congress of Cardiology(Abstract). 229- (1995)

Haruo Honjo：“L型钙电流的超慢失活负责窦房结的过度驱动抑制”第11届亚太心脏病学大会（摘要）。