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 muscle cells enzymatically dispersed from rabbit cerebral, celiac, femoral, and main pulmonary arteries, as well as from tho porcine coronary artery. In all myocyte classes examined, a reduction of Po-2 (hypoxia) produced a rapid and reversible inhibition of the macroscopic L-type Ca2+ current of similar general characteristics. The hypoxic inhibition of Ca2+ channel activity closely followed the time course of bath exchange, first becoming apparent at below similar to 80 mmHg Po-2. The interaction O-2 with the Ca2+ channels was strongly voltage dependent. At -30 mV the average extent of current inhibition was similar to 80%: however, no enter ol even potentiation of current amplitude was observed at potentials more positive than +30 mV. Hyoxia selectively slowed activation kinetics (similar to 1.5 times at -20 mV); however channel deactivation and inactivation were unaltered by low Po-2. In addition, hypoxia produced a reversible shift (8.1 +/- 1.0 mV, n = 12) of the Ca2+ conductance-voltage curve toward positive membrane potentials. We propose that the O-2 sensitivity of Ca2+ channels may contribute to the well-known hypoxic dilatation of systemic and the main pulmonary arteries.