Low po2 inhibits calcium channel activity in arterial smooth muscle
cells.
Franco-Obreg[grave]un, Alfredo, and Jos[umlaut]a L[grave]upez-Barneo.
Departamento de Fisiologaea M[umlaut]adica y Biofaesica, Facultad
de Medicina, Avenida S[cedilla]cnchez Pizju[cedilla]cn, 4, E-41009
Seville (Spain)
APStracts 3:0232H, 1996.
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 PO2 values
below 80 mm Hg. The interaction of O2 with the calcium channels was
strongly voltage-dependent. At -30 mV the average extent of current
inhibition was 80%; however no effect or even potentiation of current
amplitude was observed at potentials more positive than +30 mV.
Hypoxia selectively slowed activation kinetics (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 calcium 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.
Received 15 February 1996; accepted in final form 24 May 1996.
APS Manuscript Number H158-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96