Transient-outward K+ channel inhibition facilitates L-type Ca2+ current in heart

Journal of Cardiovascular Electrophysiology
Yanggan WangJoseph A Hill

Abstract

Transient outward current (I(to)) and L-type calcium current (I(Ca)) are important repolarization currents in cardiac myocytes. These two currents often undergo disease-related remodeling while other currents are spared, suggesting a functional coupling between them. Here, we investigated the effects of I(to) channel blockers, 4-aminopyridine (4-AP) and heteropodatoxin-2 (HpTx2), on I(Ca) in cardiac ventricular myocytes. I(Ca) was recorded in enzymatically dissociated mouse and guinea pig ventricular myocytes using the whole-cell voltage clamp method. In mouse ventricular myocytes, 4-AP (2 mM) significantly facilitated I(Ca) by increasing current amplitude and slowing inactivation. These effects were not voltage-dependent. Similar facilitating effects were seen when equimolar Ba2+ was substituted for external Ca2+, indicating that Ca2+ influx is not required. Measurements of Ca2+/calmodulin-dependent protein kinase (CaMKII) activity revealed significant increases in cells treated with 4-AP. Pretreatment of cells with 10 microM KN93, a specific inhibitor of CaMKII, abolished the effects of 4-AP on I(Ca.) To test the requirement of I(to), we studied guinea pig ventricular myocytes, which do not express I(to) channels. In these ce...Continue Reading

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Citations

Dec 15, 2010·European Heart Journal·Thitima KeskanokwongYanggan Wang
Apr 1, 2009·Journal of Cardiovascular Pharmacology·Donald M Bers, Eleonora Grandi
Apr 10, 2009·Molecular Pharmacology·Christopher V DeSimoneMichael J Morales
Jul 1, 2014·Evidence-based Complementary and Alternative Medicine : ECAM·Mônica Santos de MeloLucindo José Quintans-Júnior
Jul 6, 2007·The European Journal of Neuroscience·Jian ShiSteven G Kernie
May 28, 2014·Basic & Clinical Pharmacology & Toxicology·José Evaldo Rodrigues de Menezes-FilhoCarla Maria Lins de Vasconcelos
Jan 26, 2010·Journal of Molecular and Cellular Cardiology·Yanggan Wang, Joseph A Hill
Feb 1, 2011·Journal of Molecular and Cellular Cardiology·Mark E AndersonDonald M Bers

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