Role of calcium-activated chloride current in regulating pulmonary vasomotor tone

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83 Scopus citations

Abstract

Many agonists induce vasoconstriction by releasing intracellularly stored Ca2+ and promoting Ca2+ influx. Activation of Ca2+-activated Cl- (Cl(Ca)) channels may be a critical mechanism by which a rise in intracellular free Ca2+ concentration ([Ca2+](i)) causes membrane depolarization that serves to sustain the elevated [Ca2+ ](i) and maintain vascular tone. In this study the biophysical and pharmacological properties of Cl(Ca) currents [I(Cl(Ca))] were characterized in rat pulmonary artery (PA) smooth muscle cells, and their relationship to the regulation of pulmonary vascular tone was determined. When K+ currents were eliminated by using Cs+-containing internal solution, depolarization elicited an inward Ca2+ current followed by a time-dependent outward Cl- current that reversed near Cl- equilibrium potential. Repolarizing voltage steps produced a large inward tail Cl- current that also reversed at a potential close to Cl- equilibrium potential. Replacement of extracellular Ca2+ with Ba2+ significantly augmented the Ca2+ current but abolished the Cl- currents. The Cl- channel blocker niflumic acid (10-50 μM) diminished the time- dependent outward Cl- current and the inward tail Cl- current, decreased serotonin-induced membrane depolarization, and inhibited agonist-induced PA contraction. In the absence of extracellular Ca2+, cyclopiazonic acid, which releases Ca2+ from sarcoplasmic reticulum, elicited an inward Cl- current at a holding potential of -70 mV. These results indicate that rat PA myocytes possess Cl(Ca) channels that are activated by depolarization- induced Ca2+ influx and agonist-induced Ca2+ release. This Cl- current contributes to agonist-induced pulmonary vasoconstriction via membrane depolarization.

Original languageEnglish (US)
Pages (from-to)L959-L968
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume272
Issue number5 16-5
DOIs
StatePublished - May 1997

Keywords

  • Agonist-induced depolarization
  • Chloride channels
  • Membrane potential
  • Pulmonary arterial contraction
  • Pulmonary artery

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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