Ca(2+)-dependent components of inactivation of unitary cardiac L-type Ca(2+) channels.

The Journal of Physiology
Ira R JosephsonMichael D Stern

Abstract

A Ca(2+) ion-dependent inactivation (CDI) of L-type Ca(2+) channels (LCC) is vital in limiting and shaping local Ca(2+) ion signalling in a variety of excitable cell types. However, under physiological conditions the unitary LCC properties that underlie macroscopic inactivation are unclear. Towards this end, we have probed the gating kinetics of individual cardiac LCCs recorded with a physiological Ca(2+) ion concentration (2 mM) permeating the channel, and in the absence of channel agonists. Upon depolarization the ensemble-averaged LCC current decayed with a fast and a slow exponential component. We analysed the unitary behaviour responsible for this biphasic decay by means of a novel kinetic dissection of LCC gating parameters. We found that inactivation was caused by a rapid decrease in the frequency of LCC reopening, and a slower decline in mean open time of the LCC. In contrast, with barium ions permeating the channel ensemble-averaged currents displayed only a single, slow exponential decay and little time dependence of the LCC open time. Our results demonstrate that the fast and slow phases of macroscopic inactivation reflect the distinct time courses for the decline in the frequency of LCC reopening and the open dwell ...Continue Reading

References

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Citations

Nov 2, 2011·The Journal of General Physiology·Noriko SaegusaKenneth W Spitzer
Apr 4, 2017·Journal of Molecular and Cellular Cardiology·Claire Y ZhaoRaimond L Winslow
Dec 2, 2009·The Journal of Physiology·Jan Matthes, Stefan Herzig
May 12, 2010·Biochemical and Biophysical Research Communications·Ira R JosephsonMichael D Stern

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