The development of L‑type Ca2+ current mediated alternans does not depend on the restitution slope in canine ventricular myocardium

Tóth, Noémi and Szlovák, Jozefina and Kohajda, Zsófia and Bitay, Gergő and Veress, Roland and Horváth, Balázs and Papp, Julius Gy. and Varró, András and Nagy, Norbert (2021) The development of L‑type Ca2+ current mediated alternans does not depend on the restitution slope in canine ventricular myocardium. SCIENTIFIC REPORTS. ISSN 2045-2322

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Abstract

Cardiac alternans have crucial importance in the onset of ventricular fibrillation. The early explanation for alternans development was the voltage‑driven mechanism, where the action potential (AP) restitution steepness was considered as crucial determining factor. Recent results suggest that restitution slope is an inadequate predictor for alternans development, but several studies still claim the role of membrane potential as underlying mechanism of alternans. These controversial data indicate that the relationship of restitution and alternans development is not completely understood. APs were measured by conventional microelectrode technique from canine right ventricular papillary muscles. Ionic currents combined with fluorescent measurements were recorded by patch‑clamp technique. APs combined with fluorescent measurements were monitored by sharp microelectrodes. Rapid pacing evoked restitution‑independent AP duration (APD) alternans. When non‑alternating AP voltage command was used, Ca2+i‑transient (CaT) alternans were not observed. When alternating rectangular voltage pulses were applied, CaT alternans were proportional to ICaL amplitude alternans. Selective ICaL inhibition did not influence the fast phase of APD restitution. In this study we found that ICaL has minor contribution in shaping the fast phase of restitution curve suggesting that ICaL—if it plays important role in the alternans mechanism—could be an additional factor that attenuates the reliability of APD restitution slope to predict alternans.

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