Inactivation of the calcium current is involved in overdrive suppression of rabbit sinoatrial node cells

Eiichi Watanabe, Haruo Honjo, Mark R. Boyett, Itsuo Kodama, Junji Toyama

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Abstract

The contribution of inactivation of the L-type Ca2+ current (i(Ca) to overdrive suppression was investigated in rabbit sinoatrial (SA) node cells by use of the whole cell patch-clamp technique. In the current-clamp mode, rapid stimulation (6.7 Hz) for 30 s was followed by a transient increase in the cycle length of spontaneous action potentials of 135 ± 52% (n = 3), i.e., 'overdrive suppression.'The i(Ca) was measured in the voltage-clamp mode in the presence of 30 μM tetrodotoxin. An increase in the rate of depolarizing pulses (to 0 mV for 100 ms) 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); after 30 s of stimulation at 6.7 Hz, i(Ca) was reduced to 15.5 ± 1.8% (n = 4) of the control at 1 Hz. With an HP of -80 mV, a similar increase in the pulse rate caused much less reduction in i(Ca). When spontaneous action potentials were interrupted by a 30-s train of high- frequency voltage-clamp pulses (to 0 mV for 100 ms; 6.7 Hz) from an HP of - 40 mV, 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, a similar interruption by high-frequency voltage-clamp pulses from an HP of -80 mV caused no decrease in i(Ca), and there was no suppression of spontaneous activity after the train. Neither delayed rectifier K+ current nor hyperpolarization-activated current was affected after a train of high- frequency voltage-clamp pulses. These findings 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).

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume271
Issue number5 40-5
Publication statusPublished - 01-11-1996

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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