HYPOXIA INHIBITS THE RECOMBINANT ALPHA(1C) SUBUNIT OF THE HUMAN CARDIAC L-TYPE CA2+ CHANNEL

1. Whole-cell patch clamp recordings were used to investigate the effe cts of hypoxia on recombinant human L-type Ca2+ channel alpha(1C) subu nits stably expressed in human embryonic kidney (HEK 293) cells. 2. Ca 2+ channel currents were reversibly inhibited hypoxia (P-O2 < 90 mmHg) . The degree of inhibition depended on the charge carrier used, Ca2+ c urrents being more O-2 sensitive than Ba2+ currents. 3. Hypoxic inhibi tion of Ca2+ channel currents was more pronounced at lower activating membrane potentials (less than or equal to +30 mV), and was associated with a slowing of activation kinetics. Current inactivation and deact ivation were unaffected by hypoxia. 4. Since hypoxia similarly regulat es native L-type Ca2+ channels in vascular smooth muscle cells, our re sults suggest that hypoxic regulation of L-type Ca2+ channels arises f rom modification of structural features of the alpha(1) subunit common to cardiac and smooth muscle L-type channels.