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

TY - JOUR

T1 - Mechanism of effect of extracellular pH on L-type Ca2+ channel currents in human mesenteric arterial cells

AU - Smirnov, S V

AU - Knock, G A

AU - Belevych, A E

AU - Aaronson, P I

PY - 2000

Y1 - 2000

N2 - Extracellular pH (pH(o)) influences vasoconstriction partly by modulating Ca2+ influx through voltage-gated Ca2+ channels in the vasculature. The mechanism of this effect of pH(o) is, however, controversial. Using the whole cell voltage-clamp technique, we examined the influence of pH(o) 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 similar to 50% and increased by 25-30%, respectively, the peak amplitude of Ca2+ and Ba2+ currents (1.5 and 10 mM), with an apparent pK(a) 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.

AB - Extracellular pH (pH(o)) influences vasoconstriction partly by modulating Ca2+ influx through voltage-gated Ca2+ channels in the vasculature. The mechanism of this effect of pH(o) is, however, controversial. Using the whole cell voltage-clamp technique, we examined the influence of pH(o) 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 similar to 50% and increased by 25-30%, respectively, the peak amplitude of Ca2+ and Ba2+ currents (1.5 and 10 mM), with an apparent pK(a) 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.

UR - http://www.scopus.com/inward/record.url?scp=0033855511&partnerID=8YFLogxK

M3 - Article

SN - 1522-1539

VL - 279

SP - H76 - H85

JO - AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

JF - AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY

IS - 1

ER -