Theoretical study of L-type Ca(2+) current inactivation kinetics during action potential repolarization and early afterdepolarizations.

The Journal of Physiology
Stefano MorottiDonald M Bers

Abstract

Sarcoplasmic reticulum (SR) Ca(2+) release mediates excitation–contraction coupling (ECC) in cardiac myocytes. It is triggered upon membrane depolarization by entry of Ca(2+) via L-type Ca(2+) channels (LTCCs), which undergo both voltage- and Ca(2+)-dependent inactivation (VDI and CDI, respectively). We developed improved models of L-type Ca(2+) current and SR Ca(2+) release within the framework of the Shannon-Bers rabbit ventricular action potential (AP) model. The formulation of SR Ca(2+) release was modified to reproduce high ECC gain at negative membrane voltages. An existing LTCC model was extended to reflect more faithfully contributions of CDI and VDI to total inactivation. Ba(2+) current inactivation included an ion-dependent component (albeit small compared with CDI), in addition to pure VDI. Under physiological conditions (during an AP) LTCC inactivates predominantly via CDI, which is controlled mostly by SR Ca(2+) release during the initial AP phase, but by Ca(2+) through LTCCs for the remaining part. Simulations of decreased CDI or K(+) channel block predicted the occurrence of early and delayed after depolarizations. Our model accurately describes ECC and allows dissection of the relative contributions of different...Continue Reading

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Citations

May 28, 2014·The Journal of General Physiology·Manu Ben-Johny, David T Yue
Oct 7, 2015·Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology·Kerry L Kubly, Jonathan A W Stecyk
Jul 6, 2014·Frontiers in Pharmacology·Donald M Bers, Stefano Morotti
May 9, 2013·The Journal of Physiology·C H OrchardA F James
Apr 21, 2019·The Journal of General Physiology·Maedeh Bazmi, Ariel L Escobar
Nov 25, 2018·The Journal of General Physiology·Worawan B LimpitikulRaimond L Winslow
Mar 1, 2019·The Journal of General Physiology·Danna MoralesDiego Varela
Sep 19, 2012·The Journal of Physiology·Nicolas P SmithDavid J Paterson
Nov 14, 2018·Frontiers in Physiology·Raffaele CoppiniElisabetta Cerbai
Jul 17, 2021·The Journal of General Physiology·Brooke M AhernJonathan Satin
Oct 27, 2021·The Journal of General Physiology·Marina AngeliniRiccardo Olcese

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