Calcium‐activated transient membrane currents are carried mainly by chloride ions in isolated atrial, ventricular and Purkinje cells of rabbit heart

Abstract

SUMMARYUnder physiological conditions, calcium-dependent ([Ca2+] -dependent) Cl-currents (ICI(Ca)) have been suggested to participate in the repolarizing processes. In this paper, the possible contribution of ICl(Ca) to transient inward currents and, hence to arrhythmias, has been studied in myocytes from the working myocardium and from the conductive system. Single atrial, ventricular and Purkinje cells, isolated enzymatically from rabbit heart, have been studied under whole-cell voltage-clamp and were internally perfused with the fluorescent Ca2+ indicator, fura-2 (100 /sM). Ca + release from the sarcoplasmic reticulum was either induced by external application of caffeine or occurred spontaneously in Ca2+-overloaded cells. Membrane currents accompanying Ca2+ transients showed linear current-voltage characteristics between -60 and +80 mV as evidenced from fast voltage ramps. When intra-and extracellular Cl-concentrations were kept symmetrical in the absence of the Na+-Ca2' exchange mechanism, transient currents had a reversal potential close to 0 mV.

9–Anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential

“…In case of 9-AC, much less information is available regarding its I Cl(Ca) inhibitory action in direct current measurements. Approximately 90 % reduction was reported by Szigeti et al (1998) in rabbit heart by 0.5 mM 9-AC. In rat uterine myocytes, 0.1 mM 9-AC greatly reduced I Cl(Ca) (Jones et al 2004).…”

“…Concentrations of 9-AC were ranging from 0.1 to 1 mM to achieve chloride channel inhibition in the literature (Szigeti et al 1998;Walsh and Wang 1996). The reduction in phase-1 magnitude just as the lengthening of AP was saturated at 0.5 mM of 9-AC as 1 mM 9-AC did not increase these changes much further (both APD 90 and phase-1 magnitude values did not differ significantly in the presence of 0.5 and 1 mM 9-AC, Fig.…”

Burst Emergence of Intracellular Ca 2+ Waves Evokes Arrhythmogenic Oscillatory Depolarization via the Na + –Ca 2+ Exchanger

“…[1][2][3][4][5] Previous electrophysiological studies in isolated ventricular myocytes suggested that CaWs can evoke triggered arrhythmias by generating oscillatory depolarization via Ca 2ϩ -activated transient inward currents, 5 which consist of the Na ϩ -Ca 2ϩ exchanger (NCX) current 6,7 and other Ca 2ϩ -activated currents. 8,9 When the depolarized membrane potential (V m ) reaches the threshold of firing, myocytes exhibit nondriven action potentials (APs) and subsequent oscillations called triggered activity and delayed afterdepolarizations (DADs), respectively. 6,10 -12 Although extensive studies have been conducted on CaWs for their electrogenic and proarrhythmic potentials, most studies were focused on isolated cardiomyocytes or small excised preparations for simultaneous microelectrode recording of electric activities and Ca 2ϩ -mediated contractile force.…”

Ca2+-activated chloride channel activity during Ca2+alternans in ventricular myocytes

“…42 In the heart CaCCs have been described in various species including mouse, 43 rabbit, 12,41,44 ferret, 45 sheep, 46 dog 47 and pig. 48 During excitation activation of CaCCs together with K C channels results in a transient outward current (I to ) that plays an important role in phase 1 repolarization of the AP.…”

“…48 During excitation activation of CaCCs together with K C channels results in a transient outward current (I to ) that plays an important role in phase 1 repolarization of the AP. 41,[48][49][50] The complete understanding of CaCC function is hampered by the fact that the molecular nature of CaCCs in cardiac tissues has not been identified yet. Members of the bestrophin protein family and anoctamin-1 (Ano-1, also known as transmembrane member 16A, TMEM16A) have been proposed as putative candidates.…”