LOW PO2 INHIBITS CALCIUM-CHANNEL ACTIVITY IN ARTERIAL SMOOTH-MUSCLE CELLS

We studied the effect of O-2 tension (Po-2) on the activity of voltage -gated Ca2+ channels recorded in whole cell patch-clamped smooth muscl e cells enzymatically dispersed from rabbit cerebral, celiac, femoral, and main pulmonary arteries, as well as from tho porcine coronary art ery. In all myocyte classes examined, a reduction of Po-2 (hypoxia) pr oduced a rapid and reversible inhibition of the macroscopic L-type Ca2 + current of similar general characteristics. The hypoxic inhibition o f Ca2+ channel activity closely followed the time course of bath excha nge, first becoming apparent at below similar to 80 mmHg Po-2. The int eraction O-2 with the Ca2+ channels was strongly voltage dependent. At -30 mV the average extent of current inhibition was similar to 80%: h owever, no enter ol even potentiation of current amplitude was observe d at potentials more positive than +30 mV. Hyoxia selectively slowed a ctivation kinetics (similar to 1.5 times at -20 mV); however channel d eactivation and inactivation were unaltered by low Po-2. In addition, hypoxia produced a reversible shift (8.1 +/- 1.0 mV, n = 12) of the Ca 2+ conductance-voltage curve toward positive membrane potentials. We p ropose that the O-2 sensitivity of Ca2+ channels may contribute to the well-known hypoxic dilatation of systemic and the main pulmonary arte ries.