Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation

Abstract

We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering 02 tension (P02) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations of cytosolic Ca22+ whose frequency depends on extracellular Ca2+ influx. Switching from a P02 of 150 to 20 mmHg leads to a reversible attenuation of the Ca2' oscillations. In voltage-clamped cells, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low P02 selectively inhibits L-type Ca2' channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low P02 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of 02- sensitive, voltage-dependent, Ca2' channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.