Ion-dependent inactivation of barium current through L-type calcium channels.
It is widely believed that Ba2+ 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 gating currents of rabbit cardiac Ca2+ channels expressed in different subunit combinations in tsA201 cells, we found a phase of Ba2+ current decay with characteristics of ion-dependent inactivation. Upon a long duration (20 s) depolarizing pulse, IBa decayed as the sum of two exponentials. The slow phase (tau approximately 6 s, 21 degrees C) was parallel to a reduction of gating charge mobile at positive voltages, which was determined in the same cells. The fast phase of current decay (tau approximately 600 ms), involving about 50% of total decay, was not accompanied by decrease of gating currents. Its amplitude depended on voltage with a characteristic U-shape, reflecting reduction of inactivation at positive 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 depolarizing pulse was not due to changes in the concentration gradients driving ion movement, because Ba2+ entry during the pulse did not change the reversal potential for Ba2+. A simple model of Ca(2+) -dependent inactivation (Shirokov, R., R. Levis, N. Shirokova, and F., Ríos. 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 subunit to be 100 times lower for Ba2+ than Ca2+.
Ferreira
G
G
Department of Molecular Biophysics and Physiology, Rush University, Chicago, Illinois 60612, USA.
Yi
J
J
Ríos
E
E
Shirokov
R
R
D000818:Animals; D001464:Barium / Q000378:metabolism*; D001711:Biotransformation; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004558:Electric Stimulation; D004594:Electrophysiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D012964:Sodium / Q000378:metabolism; D014162:Transfection
D015220:Calcium Channels; D001464:Barium; D012964:Sodium