Contribution of Na+/Ca2+ exchange to action potential of human atrial myocytes

Abstract

The Ca2+ dye indo 1 was used to record internal Ca2+ (Cai) transients in order to investigate the role of the Na+/Ca2+ exchange current (INa/Ca) in whole cell patch-clamped human atrial myocytes After the activation of the L-type Ca2+ current by test pulses (20 ms) at +20 mV, a tail current (I(tail)) was activated at a holding potential of -80 mV with a density of -1.29 +/- 0.06 pA/pF. The time course of I(tail) followed that of Cai transients I(tail) was suppressed by dialyzing cells with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, applying 5 mM caffeine, or substituting external Na+ with Li+, indicating that this current was mainly generated by INa/Ca. Two types of action potential were recorded: type A, which is characterized by a narrow early plateau followed by a late low plateau phase, and type B, which is characterized by a small initial peak followed by a prolonged high plateau phase. Type B action potentials were found in larger cells than type A action potentials (membrane capacitance 81.8 +/- 4.5 and 122.4 +/- 7.0 pF in types A and B, respectively, P < 0.001). Substitution of external Na+ with Li+ shortened the late plateau of the type A action potential and the prolonged plateau of the type B action potential. Suppression of Cai transients by caffeine shortens the late part of both types of action potentials, whereas its lengthening effect on the initial phase of action potentials can result from several different mechanisms. The beat-to-beat dependent relationship between Cai transients and action potentials could be mediated by Ina/Ca- Delayed afterdepolarizations were present in a significant proportion of atrial myocytes in our experimental conditions. They were reversibly suppressed by Li+ substitution for Na+, suggesting that they are generated by INa/Ca. We conclude that INa/Ca plays a major role in the development of action potentials and delayed afterdepolarizations in isolated human atrial myocytes.

Molecular Determinants of Altered Ca 2+ Handling in Human Chronic Atrial Fibrillation

“…Thus, the higher phosphorylation of RyR2 and PLB together with the upregulation of NCX1 (present study) 17,21 may represent the molecular correlate of triggered activity mediated by late afterdepolarizations. 49 We identified impaired MyBP-C phosphorylation as a potential novel molecular mechanism for contractile dysfunction, which is one major contributor to atrial thrombogenesis. Because positive inotropic drugs exhibit low efficacy and cause arrhythmias, restoration of MyBP-C phosphorylation may be a promising therapeutic target to improve atrial contractility in the postcardioversion period.…”

Effects of Experimental Heart Failure on Atrial Cellular and Ionic Electrophysiology

“…The NCX is known to carry transient inward currents that cause DADs and triggered activity. 14,25 Stambler and coworkers have observed atrial tachycardias with properties of triggered arrhythmias in dogs with CHF, 25a to which increased NCX could well be an important contributor. AF is readily induced in CHF dogs by atrial burst pacing but not by single extrastimuli.…”

Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+

“…contributes to the duration of the action potential and to the generation of delayed afterdepolarizations [11,12]. 21 The first description of a [Ca ] -dependent nonselective 21 i In situations of [Ca ] [1]).…”