| Co-Investigator(Kenkyū-buntansha) |
HORIBA Isao Meijo Univ., Faculty of Sci.and Techno., Assistant Professor, 理工学部, 助教授 (60199560)
TOYAMA Junji Nagoya Univ., Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (20023658)
KODAMA Itsuo Nagoya Univ., Res.Inst.of Environ.Med., Professor, 環境医学研究所, 教授 (30124720)
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| Research Abstract |
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>.
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