Ionic mechanisms underlying overdrive suppression of sinoatrial node cells

窦房结起搏细胞的自发活动在快速驱动时受到短暂抑制，这种现象被称为“自发抑制”。虽然提出了若干机制，但仍有许多问题有待澄清。最近Boyett等人表明，在心室细胞中，刺激速率的增加导致L-型钙电流（I）的突然下降，随后缓慢下降<Ca>。I_2的缓慢下降<Ca>被解释为I_2的超缓慢电压依赖性失活<ca>。本研究<Ca>应用全细胞钳夹技术研究了I_2失活对兔窦房结细胞抑制的作用。在电流钳模式下，快速刺激（6.7Hz）后，自发活动的短暂抑制。在电压钳模式下，当保持电位（HP）为-40 mV时，去极化速率从1 Hz增加到6.7 Hz时，I_2突然下降，然后逐渐下降<Ca>。在HP为-80 mV时，脉冲频率的增加引起的I_的减少要少得多<Ca>。当自发动作电位被一串高频脉冲（6.7Hz）从-40mV的HP中断时，在该串期间I_（max）再次显著降低<Ca>，在该串之后，自发活动有短暂的抑制。相反，由-80mV的HP的高频脉冲中断不会引起I_2的降低，<Ca>并且在训练后不会抑制自发活动。高频脉冲串对延迟整流钾电流和超极化激活电流均无影响。这些结果表明，SA结中的I_2抑制至少部分是I_2的速率和电压依赖性失活的结果<Ca>。

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>.