Low PO2 inhibits calcium channel activity in arterial smooth muscle cells.
We studied the effect of O2 tension (PO2) 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 the porcine coronary artery. In all myocyte classes examined, a reduction of PO2 (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 approximately 80 mmHg PO2. The interaction of O2 with the Ca2+ channels was strongly voltage dependent. At -30 mV the average extent of current inhibition was approximately 80%; however, no effect or even potentiation of current amplitude was observed at potentials more positive than +30 mV. Hypoxia selectively slowed activation kinetics (approximately 1.5 times at -20 mV); however, channel deactivation and inactivation were unaltered by low PO2. 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 O2 sensitivity of Ca2+ channels may contribute to the well-known hypoxic dilatation of systemic and the main pulmonary arteries.
Franco-Obregón
A
A
Departamento de Fisiología Médica y Biofísica, Facultad de Medicina, Seville, Spain.
López-Barneo
J
J
D000818:Animals; D001158:Arteries / Q000166:cytology / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D004594:Electrophysiology; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism* / Q000502:physiology; D010313:Partial Pressure; D011817:Rabbits; D013997:Time Factors
D015220:Calcium Channels; D010100:Oxygen