Oxygen-sensitive calcium channels in vascular smooth muscle and their possible role in hypoxic arterial relaxation.
We have investigated the modifications of cytosolic [Ca2+] and the activity of Ca2+ channels in freshly dispersed arterial myocytes to test whether lowering O2 tension (PO2) directly influences Ca2+ homeostasis in these cells. Unclamped cells loaded with fura-2 AM exhibit oscillations 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, hypoxia reversibly reduces the influx of Ca2+ through voltage-dependent channels, which can account for the inhibition of the Ca2+ oscillations. Low PO2 selectively inhibits L-type Ca2+ channel activity, whereas the current mediated by T-type channels is unaltered by hypoxia. The effect of low PO2 on the L-type channels is markedly voltage dependent, being more apparent with moderate depolarizations. These findings demonstrate the existence of O2-sensitive, voltage-dependent, Ca2+ channels in vascular smooth muscle that may critically contribute to the local regulation of circulation.
Franco-Obregón
A
A
Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Facultad de Medicina, Spain.
Ureña
J
J
López-Barneo
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002445:Celiac Artery / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D016257:Fura-2 / Q000031:analogs & derivatives; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010313:Partial Pressure; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013997:Time Factors
D015220:Calcium Channels; D005456:Fluorescent Dyes; C049925:fura-2-am; D004533:Egtazic Acid; D009543:Nifedipine; D011188:Potassium; D010100:Oxygen; D002118:Calcium; D016257:Fura-2