Changes of calcium channel inactivation during run-down

Run down of calcium channel currents carried by Ba2+ was studied in enzymatically isolated ventricular cells from guinea-pig hearts using the suction pipette method. The decay of the Ba currents elicited by 100 ms voltage steps from -60 to 0 mV could be best described biexponentially. The peak current amplitude declined monotonously during dialysis of cell interior, whereas the inactivation showed a biphasic behaviour. After start of intracellular perfusion, the time constants of the fast and slow exponential component decreased up to the 6th and 10th minute, respectively. Thereafter the inactivation decelerated. These changes of the inactivation behaviour could be described by a model of current dependent inactivation. It was assumed, that in the first phase the decay is accelerated due to predominating of washout of phosphorylating agents and in the second phase the reduced conductance of the cell membrane for Ba2+ due to progressive irreversible closure of Ca channels causes slowing down of inactivation.