Ca 2+ -Induced Current Oscillations in Rabbit Ventricular Myocytes

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Abstract
Transient currents are activated by spontaneous Ca2+ oscillations in rabbit ventricular myocytes. We investigated the ionic basis for these transient currents under conditions in which K+ currents would be expected to be blocked. Holding cells under voltage clamp at positive potentials leads to a rise in intracellular Ca2+ via reversal of the Na+-Ca2+ exchanger and subsequently to the initiation of spontaneous Ca2+ transients, presumably from a Ca2+-overloaded sarcoplasmic reticulum. The current transients associated with these Ca2+ transients reversed at about +10 to +15 mV under conditions of approximately symmetrical Cl−. In the absence of Cl−, this current was inward at all potentials examined over the range from −88 to +72 mV, consistent with a Na+-Ca2+ exchanger current. In the absence of Na+, the repetitive spontaneous Ca2+ transients could be initiated by a brief train of depolarizations to activate the inward Ca2+ current. Under such conditions, the current was found to reverse at −3 mV when the equilibrium potential of Cl− (ECl) was −2 mV, and the reversal potential shifted to −32 mV when internal Cl− was lowered, to make ECl −33 mV. Thus, in the absence of Na+, it appears that the current is exclusively a Ca2+-activated Cl− current. There is no evidence to indicate the presence of a Ca2+-activated cationic conductance. Further, our results demonstrate that the Ca2+-activated Cl− conductance can carry inward current at potentials more negative to ECl in rabbit ventricular myocytes and is therefore likely to contribute to the arrhythmogenic delayed afterdepolarizations that occur in Ca2+-overloaded cells.