OXYGEN-SENSITIVE CALCIUM CHANNELS IN VASCULAR SMOOTH-MUSCLE AND THEIRPOSSIBLE ROLE IN HYPOXIC ARTERIAL RELAXATION

We have investigated the modifications of cytosolic [Ca2+] and the act ivity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O-2 tension (PO2) directly influences Ca2+ homeostasi s in these cells. Unclamped cells loaded with fura-2 AM exhibit oscill ations of cytosolic Ca2+ whose frequency depends on extracellular Ca2 influx. Switching from a PO2 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2+ oscillations. In voltage clamped cells, hypoxi a reversibly reduces the influx of Ca2+ through voltage-dependent chan nels, which can account for the inhibition of the Ca2+ oscillations. L ow PO2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia, The effec t of low PO2 on the L-type channels is markedly voltage dependent, bei ng more apparent with moderate depolarizations, These findings demonst rate the existence of O-2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.