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Purinergic Regulation of Transient Calcium-Dependent Chloride Current Ito2 in Rat Ventricular Myocardium

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract—

Diadenosine polyphosphates (DAP) are now considered as a new class of endogenous regulatory cardiotropic compounds. In previous studies DAP were demonstrated to affect cardiac electrical activity and contractility in various animal species including rats. DAP decreased the action potential duration and reduced the contractility of the rat myocardium. At the same time, DAP did not affect repolarizing potassium currents (IK1, IKACh, Ito1, IKur), which normally participate in repolarization after the action potentials (AP), and had a little effect on L-type calcium current in isolated rat cardiomyocytes. However, in addition to these ionic currents, AP duration can be regulated via chloride currents. In this study the presence of a transient inward calcium-dependent chloride current Ito2 has been shown in rat ventricular myocardium and an influence of DAP on this current has been demonstrated for the first time. Ionic currents were recorded in isolated rat ventricular cardiomyocytes using whole-cell patch clamp method. Action potentials were recorded in isolated preparations of rat right ventricle with sharp glass microelectrodes. In the absence of Na+ and K+ and in the presence of potassium current blockers 4-aminopyridine (5 × 10–3 M) and tetraethylammonium (1.5 × 10–2 M) transient outward current was present in ventricular myocytes. This current was sensitive to non-selective chloride channel blocker 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS, 10–5 M), L-type calcium current blocker nifedipine (10–5 M), and a selective blocker of calcium-dependent chloride channels 6-(1,1-dimethyl ethyl ethyl)-2-[(2-furanyl carbonyl)amino]-4,5,6,7-tetrahydrobenzo[b]thiophen-3 carbonic acid (CaCCinh-A01, 10–5 M). In the presence of diadenosine tetraphosphate (Ap4A, 10–4 M) in the external solution the peak amplitude of the current increased by 44 ± 11%. Diadenosine pentaphosphate (Ap5A) and NAD+ failed to produce any significant effects on the current density. In isolated preparations of rat ventricular myocardium DIDS (10–5 M) and CaCCinh-A01 (10–5 M) blocked the Ap4A-induced acceleration of repolarization. Thus, the effects of Ap4A on cardiac electrical activity in rats are at least partially mediated by its influence on the amplitude of repolarizing chloride current Ito2.

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Authors and Affiliations

  1. Moscow Lomonosov State University, 119234, Moscow, Russia

    T. S. Filatova & D. V. Abramochkin

  2. Pirogov Russian National Research Medical University, 117997, Moscow, Russia

    T. S. Filatova & D. V. Abramochkin

  3. Laboratory of Cardiac Physiology, Institute of Physiology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 167982, Syktyvkar, Komi Republik, Russia

    D. V. Abramochkin

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  1. T. S. Filatova
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Correspondence to T. S. Filatova.

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Translated by T. Filatova

Abbreviations: AP, action potential; DAP, diadenosine polyphosphates; TEA, tetraethylammonium; 4-AP, 4-aminopyridine.

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Filatova, T.S., Abramochkin, D.V. Purinergic Regulation of Transient Calcium-Dependent Chloride Current Ito2 in Rat Ventricular Myocardium. Biochem. Moscow Suppl. Ser. A 13, 147–154 (2019). https://doi.org/10.1134/S1990747818060041

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  • DOI: https://doi.org/10.1134/S1990747818060041

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