Slow inward current in single cells isolated from adult human ventricles |
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Authors: | Jean -Pierre Bénitah Patrick Bailly Marie -Claire D'Agrosa Jean -Philippe Da Ponte Carmen Delgado Paco Lorente |
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Affiliation: | (1) Faculté de Médecine, U 195 INSERM, Place Henri Dunant, BP 38, F-63 001 Clermont-Ferrand, France;(2) Service de Chirurgie Cardiovasculaire du CHRU Saint-Jacques, Clermont-Ferrand, France;(3) Departamento de Farmacología y Toxicología, Universidad Complutense, Madrid, Spain |
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Abstract: | Characteristics of the slow inward current (Isi) in human ventricular myocytes isolated from septal specimens obtained in patients undergoing corrective cardiac surgery were studied using the whole-cell clamp method. A first series of experiments was performed under normal standard superfusion. Clamping from –60 mV evoked an inward current with a threshold at about –35 mV, a maximum around +10 mV and an apparent reversal potential at about +55 mV. No overlapping transient or background outward currents were detected in the –60 to +30 mV potential range, but time-dependent and steady-state outward currents were elicited at potentials above +30 mV. An overlap of steady-state activation and inactivation curves was present between –30 and +10 mV and a slight relief from inactivation was observed for voltages positive to +10mV. The time course of inactivation consisted of fast and slow phases with time constants differing by a factor of eight. Slow time constants of inactivation were shorter at potentials that elicited larger Isi, and longer at potentials inducing smaller Isi. Recovery from inactivation evolved slowly with 100% reactivation occurring in about 4000 ms. Switching the holding potential from –60 to –40 mV led to a reversible decline of Isi without any change of the decay time constants. Isi was significantly increased by 0.1 M isoproterenol. Total or partial inhibition by inorganic (2 mM Mn2+, 3 mM Co2+, 1 mM Cd2+) and organic (1 M methoxyverapamil, 5 M diltiazem) calcium antagonists did not unmask any transient outward current. However, a consistent increase of Isi was reversibly observed with 3 mM 4-aminopyridine while using standard solutions. A second series of experiments carried out with K+- and Na+-free solutions did not demonstrate any significant change from data observed with standard solutions except a reduction of outward currents at steps above +30 mV and alteration of inactivation kinetics. In this experimental setting, 4-aminopyridine also increased Isi but to a lesser degree. We conclude that Isi, as compared to the outward currents, is dominant in the diseased human ventricular cells we have studied. |
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Keywords: | Single human ventricular cell Whole-cell recording Slow inward current |
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