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Am J Physiol Cell Physiol 278: C26-C32, 2000;
0363-6143/00 $5.00
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Vol. 278, Issue 1, C26-C32, January 2000

Retardation of cation channel deactivation by mitochondrial dysfunction in adrenal medullary cells

M. Inoue, N. Fujishiro, and I. Imanaga

Department of Physiology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan

The mechanism for cyanide (CN) activation of a nonselective cation (NS) channel coupled with a muscarinic receptor in a guinea pig chromaffin cell was studied with the perforated-patch method. Bath application of a protein kinase inhibitor resulted in a dose-dependent inhibition of muscarine-induced current (IM) but had no apparent effect on the CN-induced current (ICN). On the other hand, production of ICN occluded muscarine activation of NS channels in an amplitude-dependent manner. Deactivation of IM after washout was retarded while ICN was also active, and the extent of the retardation increased with an increase in the relative production of ICN on muscarinic stimulation. Restoration of Na+ pump activity from CN suppression was conspicuously retarded below 19-20°C, and the apparent diminution of IM and ICN after washout was retarded in parallel with a decrease in temperature. The results suggest that CN activation of NS channels is due to suppression of deactivation of the channel.

muscarinic receptor; mitochondria; temperature; cyanide





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