Transient outward current in human and rat ventricular myocytes

Abstract

In a limited number of cells, I(to) in human ventricular myocytes shows no dramatic differences between cells derived from failing and non-failing hearts. The characteristics of I(to) in human cells were similar though not identical to I(to) in rat heart cells. This current may be a potential target for antiarrhythmic drug action.

Modulation of transient outward current by extracellular protons and Cd2+ in rat and human ventricular myocytes

“…One major difference was the position of steady-state activation and inactivation curves. In rat, our observations are consistent with those of others, depending on the ICa,L channel blocker used (Apkon & Nerbonne, 1991;Lefevre et al 1991;Wettwer et al 1993). The activation and inactivation curves in human cells were found at more positive membrane potentials.…”

α1-Adrenoceptors stimulate a Gαs protein and reduce the transient outward K+ current via a cAMP/PKA-mediated pathway in the rat heart

“…Because I to is the main current responsible for the duration of the action potential in the rat (2,12) and for phase 1 in humans (46), the magnitude of this current is highly regulated. In rat ventricular myocytes, the I to channel seems to be a heterotetramer composed of cloned voltage-dependent K ϩ channels Kv4.3 and Kv4.2 (39,44).…”

Human ex-vivo action potential model for pro-arrhythmia risk assessment

“…Various academic groups have used, to a very limited extent, cardiac tissues from healthy donors (Boukens et al, 2015;Jost et al, 2005Jost et al, , 2013 and patients (Brandenburger et al, 2015;Näbauer, Beuckelmann, Überfuhr, & Steinbeck, 1996;Näbauer & Kääb, 1998;Nawrath & Eckel, 1979;Sivagangabalan et al, 2014;Wettwer et al, 1993;Wettwer, Amos, Posival, & Ravens, 1994) to investigate the role of ion channels, specifically potassium channels, in human ventricular repolarization. Additionally, dofetilide, Sotalol and quinidine have been found to prolong ventricular repolarization in healthy human hearts (QT duration;Johannsen et al, 2014;Lande et al, 1998;Vicente et al, 2015) and patients (QT duration (Echt et al, 1982;McComb, McGovern, McGowan, Ruskin, & Garan, 1987); monophasic AP recordings (Melicherick et al, 1999;Nademanee et al, 1990;Yuan, Wohlfart, Rasmussen, Olsson, & Blomstrom-Lundqvist, 1994)).…”

“…While access to animal tissues is typically plentiful, the availability of human cardiac samples is limited. When available, human tissues have typically been limited to fixed or frozen samples or very small amounts of fresh and viable tissues which were obtained from surgical discards (Boukens et al, 2015;Jost et al, 2005Jost et al, , 2013Brandenburger et al, 2015;Näbauer, Beuckelmann, Überfuhr, & Steinbeck, 1996;Näbauer & Kääb, 1998;Wettwer et al, 1993;Wettwer, Amos, Posival, & Ravens, 1994). However, in the past, tissue recovery procedures, as well as tissue quality and quantity have been extremely variable, resulting in an unreliable source for robust and reproducible drug safety data.…”