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Am J Physiol Heart Circ Physiol 279: H76-H85, 2000;
0363-6135/00 $5.00
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Vol. 279, Issue 1, H76-H85, July 2000

Mechanism of effect of extracellular pH on L-type Ca2+ channel currents in human mesenteric arterial cells

Sergey V. Smirnov1, Gregory A. Knock1, Andriy E. Belevych2, and Philip I. Aaronson1

1 Division of Pharmacology and Therapeutics, Centre for Cardiovascular Biology and Medicine, King's College London, London SE1 7EH, United Kingdom; and 2 Department of Nerve-Muscle Physiology, Bogomoletz Institute of Physiology, Kiev-24, Ukraine

Extracellular pH (pHo) influences vasoconstriction partly by modulating Ca2+ influx through voltage-gated Ca2+ channels in the vasculature. The mechanism of this effect of pHo is, however, controversial. Using the whole cell voltage-clamp technique, we examined the influence of pHo on L-type Ca2+ channel currents in isolated human mesenteric arterial myocytes. Acidification to pH 6.2 and alkalinization to 8.2 from 7.2 decreased by ~50% and increased by 25-30%, respectively, the peak amplitude of Ca2+ and Ba2+ currents (1.5 and 10 mM), with an apparent pKa of 6.8. Activation and inactivation of Ca2+ and Ba2+ currents were shifted toward positive membrane voltages during acidification and in the opposite direction during alkalinization. The relationship between the current amplitude and shifts in the gating parameters in solutions of different pHo conformed closely to that predicted by the Gouy-Chapman model, in which the divalent cation concentration at the outer surface of the membrane varies with the extent to which protons neutralize the membrane surface potential.

vascular smooth muscle cells; mesenteric artery; calcium channels


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