Inactivation of the calcium current is involved in overdrive
suppression of rabbit sinoatrial node cells.
Watanabe, Ei-Ichi, Haruo Honjo, Mark R. Boyett, Itsuo Kodama, and
Junji Toyama.
Departments of Circulation and Humoral Regulation, Research
Institute of Environmental Medicine, Nagoya University, Nagoya 464
-01, Japan, Department of Physiology, University of Leeds, Leeds LS2
9JT, UK
APStracts 3:0212H, 1996.
The contribution of inactivation of the L-type Ca2+ current (iCa) to
overdrive suppression was investigated in rabbit sinoatrial (SA) node
cells using 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) - "overdrive suppression". iCa
was measured in the voltage clamp mode in the presence of 30 (M
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 iCa;
after 30 s stimulation at 6.7 Hz, iCa was reduced to 15.5 1.8 % (n=4)
of the control at 1 Hz. With a HP of -80 mV, a similar increase in
the pulse rate caused much less reduction in iCa. 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 a HP of -40
mV, there was again a marked decrease in iCa 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 a HP of -80 mV caused no decrease in iCa
and there was no suppression of spontaneous activity after the train.
Neither delayed rectifier K+ current (iK) nor hyperpolarization
-activated current (if) 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 iCa.
Received 2 October 1994; accepted in final form 26 April 1996.
APS Manuscript Number H924-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96