Contribution of L-Type Ca2+ Channels to Early Afterdepolarizations Induced by I Kr and I Ks Channel Suppression in Guinea Pig Ventricular Myocytes

Contribution of L-Type Ca2+ Channels to Early Afterdepolarizations Induced by I Kr and I Ks... Early afterdepolizations (EADs) induced by suppression of cardiac delayed rectifier I Kr and/or I Ks channels cause fatal ventricular tachyarrhythmias. In guinea pig ventricular myocytes, partial block of one of the channels with complete block of the other reproducibly induced EADs. Complete block of both I Kr and I Ks channels depolarized the take-off potential and reduced the amplitude of EADs, which in some cases were not clearly separated from the preceding action potentials. A selective L-type Ca2+ (I Ca,L) channel blocker, nifedipine, effectively suppressed EADs at submicromolar concentrations. As examined with the action potential-clamp method, I Ca,L channels mediated inward currents with a spike and dome shape during action potentials. I Ca,L currents decayed mainly due to inactivation in phase 2 and deactivation in phase 3 repolarization. When EADs were induced by complete block of I Kr channels with partial block of I Ks channels, repolarization of the action potential prior to EAD take-off failed to increase I K1 currents and thus failed to completely deactivate I Ca,L channels, which reactivated and mediated inward currents during EADs. When both I Kr and I Ks channels were completely blocked, I Ca,L channels were not deactivated and mediated sustained inward currents until the end of EADs. Under this condition, the recovery and reactivation of I Ca,L channels were absent before EADs. Therefore, an essential mechanism underlying EADs caused by suppression of the delayed rectifiers is the failure to completely deactivate I Ca,L channels. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Contribution of L-Type Ca2+ Channels to Early Afterdepolarizations Induced by I Kr and I Ks Channel Suppression in Guinea Pig Ventricular Myocytes

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Publisher
Springer-Verlag
Copyright
Copyright © 2008 by Springer Science+Business Media, LLC
Subject
Life Sciences; Human Physiology ; Biochemistry, general
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-008-9113-9
Publisher site
See Article on Publisher Site

Abstract

Early afterdepolizations (EADs) induced by suppression of cardiac delayed rectifier I Kr and/or I Ks channels cause fatal ventricular tachyarrhythmias. In guinea pig ventricular myocytes, partial block of one of the channels with complete block of the other reproducibly induced EADs. Complete block of both I Kr and I Ks channels depolarized the take-off potential and reduced the amplitude of EADs, which in some cases were not clearly separated from the preceding action potentials. A selective L-type Ca2+ (I Ca,L) channel blocker, nifedipine, effectively suppressed EADs at submicromolar concentrations. As examined with the action potential-clamp method, I Ca,L channels mediated inward currents with a spike and dome shape during action potentials. I Ca,L currents decayed mainly due to inactivation in phase 2 and deactivation in phase 3 repolarization. When EADs were induced by complete block of I Kr channels with partial block of I Ks channels, repolarization of the action potential prior to EAD take-off failed to increase I K1 currents and thus failed to completely deactivate I Ca,L channels, which reactivated and mediated inward currents during EADs. When both I Kr and I Ks channels were completely blocked, I Ca,L channels were not deactivated and mediated sustained inward currents until the end of EADs. Under this condition, the recovery and reactivation of I Ca,L channels were absent before EADs. Therefore, an essential mechanism underlying EADs caused by suppression of the delayed rectifiers is the failure to completely deactivate I Ca,L channels.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Jun 20, 2008

References

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