Ca 2+ -Induced Current Oscillations in Rabbit Ventricular Myocytes

Abstract

Abstract Transient currents are activated by spontaneous Ca 2+ 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 Ca 2+ via reversal of the Na + -Ca 2+ exchanger and subsequently to the initiation of spontaneous Ca 2+ transients, presumably from a Ca 2+ -overloaded sarcoplasmic reticulum. The current transients associated with these Ca 2+ 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 + -Ca 2+ exchanger current. In the absence of Na + , the repetitive spontaneous Ca 2+ transients could be initiated by a brief train of depolarizations to activate the inward Ca 2+ current. Under such conditions, the current was found to reverse at −3 mV when the equilibrium potential of Cl − (E Cl ) was −2 mV, and the reversal potential shifted to −32 mV when internal Cl − was lowered, to make E Cl −33 mV. Thus, in the absence of Na + , it appears that the current is exclusively a Ca 2+ -activated Cl − current. There is no evidence to indicate the presence of a Ca 2+ -activated cationic conductance. Further, our results demonstrate that the Ca 2+ -activated Cl − conductance can carry inward current at potentials more negative to E Cl in rabbit ventricular myocytes and is therefore likely to contribute to the arrhythmogenic delayed afterdepolarizations that occur in Ca 2+ -overloaded cells.