VOLTAGE-DEPENDENT KINETICS OF NA-CA EXCHANGE CURRENT IN CA2+-LOADED GUINEA-PIG HEART-CELLS

Voltage-dependent properties of Na-Ca exchange current were revealed with the patch-clamp technique in Ca2+-overloaded guinea pig ventricular myocytes in the whole cell configuration. With the assumption that the transient inward current (I(ti)) is mediated by the Na-Ca exchanger, oscillations of internal Ca2+ concentration ([Ca2+]i) were used to investigate voltage-dependent kinetics of exchange current differences at two [Ca2+]i values. After I(ti) was elicited by clamping from -45 mV to basic pulses of +10 mV, pairs of equipotential short test pulses were applied during the basic pulse at both the phase of low [Ca2+]i (between two neighboring I(ti) values) and the phase of high [Ca2+]i (at the peak of I(ti)). The test pulses were short enough to leave the time course of I(ti) during the basic pulse approximately unchanged, which allowed study of the voltage dependence of the respective current differences without disturbing the underlying oscillation of [Ca2+]i. The current differences were inward at all potentials between -140 and +70 mV, started from an equal initial value, and obeyed characteristic voltage-dependent time courses: hyperpolarization to potentials negative to -70 mV caused an initial current increase, which was followed by a decay to very small amplitudes or zero with a decay time constant decreasing toward hyperpolarization e-fold per 45.6 mV. Depolarizing pulses caused a decay of the current differences to smaller levels. Respective current differences formed during a slowly decaying current component, following the Ca current spike, showed equal voltage-dependent properties. This indicates that the slowly decaying current component is preferentially also carried by the Na-Ca exchanger. The voltage-dependent time course of the current differences is discussed to be a function of the probability of the exchanger to be in a state when Ca2+ can bind at the inside.