Slow inward tail currents in rabbit cardiac cells.

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Abstract
A whole-cell gigaseal suction microelectrode voltage-clamp technique has been used to study slow inward tail currents in single myocytes obtained by enzymatic dispersion of rabbit ventricle and atrium. A variety of stimulation protocols, Tyrode solutions and pharmacological agents have been used to test three hypotheses: (a) that the slow inward tail current is generated by an electrogenic Na+-Ca2+ exchanger; (b) that a rise in [Ca2+]i, due to release from the sarcoplasmic reticulum can modulate the activity of this exchanger; and (c) that the uptake of calcium by the sarcoplasmic reticulum is a major determinant of the time course of the tail current. In ventricular cells, the envelope of these tail currents obtained by varying the duration of the preceding depolarizations shows that (a) the tail currents are activated by pulses as short as 10 ms, and reach a maximum for pulse durations of 100-200 ms, (b) the rate of decay of the tail current gradually increases as the activating depolarizations are prolonged, and (c) the tails cannot be due to deactivation of calcium currents, in agreement with other studies in frog heart. When the mean level of [Ca2+]i is raised following inhibition of the Na+-K+ pump by strophanthidin (10-5 M) or reductions in [K+]o (0.5 mM), the slow inward tail grows in size prior to the onset of a contracture or other signs of calcium-induced toxicity. In a number of different preparations, replacement of [Ca2+]0 with BaCl2 markedly or completely inhibits the Na+-Ca2+ exchanger, whereas Sr2+ replacement does not have this effect. In myocytes from rabbit ventricle the slow inward tails are reduced significantly and decay more slowly in 0.5-2.2 mM-BaCl2 Tyrode solution, while in 2.2 mM SrCl2 these tails are not altered. The slow inward tail also shows a dependence on [K+]0, corresponding to previous data on Na+-Ca2+ exchange in other tissues. These results from rabbit ventricular and atrial cells support the hypothesis that the slow tail current reflects the electrogenic activity of the Na+-Ca2+ exchanger. However, the observed changes in the slow tail current caused by indirect manipulations of Ca2+-sequestration into the sarcoplasmic reticulum suggest that intracellular calcium homeostasis involves a complex interaction between Ca2+ sequestration into the sarcoplasmic reticulum and Ca2+ extrusion via the Na+-Ca2+ exchanger.