ION-DEPENDENT INACTIVATION OF BARIUM CURRENT THROUGH L-TYPE CALCIUM CHANNELS

It is widely believed that Bd(2+) currents carried through L-type Ca2 channels inactivate by a voltage-dependent mechanism similar to that described for other voltage-dependent channels. Studying ionic and gat ing currents of rabbit cardiac Ca2+ channels expressed in different su bunit combinations in tsA201 cells, we found a phase of Ba2+ current d ecay with characteristics of ion-dependent inactivation. Upon a long d uration (20 s) depolarizing pulse, Tga decayed as the sum of two expon entials. The slow phase (tau approximate to 6 s, 21 degrees C) was par allel to a reduction of gating charge mobile at positive voltages, whi ch was determined in the same cells. The fast phase of current decay ( 7 = 600 ms), involving about 50% of total decay, was not accompanied b y decrease of gating currents. Its amplitude depended on voltage with a characteristic U-shape, reflecting reduction of inactivation at posi tive voltages. When Na+ was used as the charge carrier, decay of ionic current followed a single exponential, of rate similar to that of the slow decay of Ba2+ current. The reduction of Ba2+ current during a de polarizing pulse was not due to changes in the concentration gradients driving ion movement, because Ba2+ entry during the pulse did not cha nge the reversal potential for Ba2+. A simple model of Ca2+-dependent inactivation (Shirokov,R,R. Levis, N. Shirokova, and E. Rios. 1993. J. Gen. Physiol. 102:1005-1030) robustly accounts for fast Ba2+ current decay assuming the affinity of the inactivation site on the alpha(1) s ubunit to be 100 times lower for Ba2+ than Ca2