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

Sergey V Smirnov, Gregory A Knock, Andriy E Belevych, Philip I Aaronson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)H76-H85
JournalAmerican Journal of Physiology-Heart and Circulatory Physiology
Volume279
Issue number1
Publication statusPublished - 2000

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Membranes
Divalent Cations
Patch-Clamp Techniques
Vasoconstriction
Membrane Potentials
Muscle Cells
Protons
Direction compound

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Mechanism of effect of extracellular pH on L-type Ca2+ channel currents in human mesenteric arterial cells. / Smirnov, Sergey V; Knock, Gregory A; Belevych, Andriy E; Aaronson, Philip I.

In: American Journal of Physiology-Heart and Circulatory Physiology, Vol. 279, No. 1, 2000, p. H76-H85.

Research output: Contribution to journalArticle

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abstract = "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.",
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AU - Aaronson, Philip I

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

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