Effect of the intracellular calcium concentration chelator BAPTA acetoxy-methylester on action potential duration in canine ventricular myocytes

Horváth, Balázs and Szentandrássy, Norbert and Veress, Roland and Baranyai, Dóra and Kistamás, Kornél and Almássy, János and Tóth, A. and Magyar, János and Bányász, Tamás and Nánási, Péter Pál (2018) Effect of the intracellular calcium concentration chelator BAPTA acetoxy-methylester on action potential duration in canine ventricular myocytes. JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 69 (1). pp. 99-107. ISSN 0867-5910

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Abstract

Intracellular calcium concentration ([Ca(2+)]i) is often buffered by using the cell-permeant acetoxy-methylester form of the Ca(2+) chelator BAPTA (BAPTA-AM) under experimental conditions. This study was designed to investigate the time-dependent actions of extracellularly applied BAPTA-AM on action potential duration (APD) in cardiac cells. Action potentials were recorded from enzymatically isolated canine ventricular myocytes with conventional sharp microelectrodes. The effect of BAPTA-AM on the rapid delayed rectifier K(+) current (IKr) was studied using conventional voltage clamp and action potential voltage clamp techniques. APD was lengthened by 5 muM BAPTA-AM - but not by BAPTA - and shortened by the Ca(2+) ionophore A23187 in a time-dependent manner. The APD-lengthening effect of BAPTA-AM was strongly suppressed in the presence of nisoldipine, and enhanced in the presence of BAY K8644, suggesting that a shift in the [Ca(2+)]i-dependent inactivation of L-type Ca(2+) current may be an important underlying mechanism. However, in the presence of the IKr-blocker dofetilide or E-4031 APD was shortened rather than lengthened by BAPTA-AM. Similarly, the APD-lengthening effect of 100 nM dofetilide was halved by the pretreatment with BAPTA-AM. In line with these results, IKr was significantly reduced by extracellularly applied BAPTA-AM under both conventional voltage clamp and action potential voltage clamp conditions. This inhibition of IKr was partially reversible and was not related to the Ca(2+) chelator effect BAPTA-AM. The possible mechanisms involved in the APD-modifying effects of BAPTA-AM are discussed. It is concluded that BAPTA-AM has to be applied carefully to control [Ca(2+)]i in whole cell systems because of its direct inhibitory action on IKr.

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