Mobilization of intracellular Ca2+ by endothelin-1 in rat intrapulmonary arterial smooth muscle cells

Research output: Contribution to journalArticle

Abstract

Endothelin-1 (ET-1) increases intracellular Ca2+ concentration ([Ca2+](i)) in pulmonary arterial smooth muscle cells (PASMCs); however, the mechanisms for Ca2+ mobilization are not clear. We determined the contributions of extracellular influx and intracellular release to the ET-1- induced Ca2+ response using Indo 1 fluorescence and electrophysiological techniques. Application of ET-1 (10-10 to 10-8 M) to transiently (24-48 h) cultured rat PASMCs caused concentration-dependent increases in [Ca2+](i). At 10-8 M, ET-1 caused a large, transient increase in [Ca2+](i) (>1 μM) followed by a sustained elevation in [Ca2+](i) (<200 nM). The ET-1-induced increase in [Ca2+](i) was attenuated (<80%) by extracellular Ca2+ removal; by verapamil, a voltage-gated Ca2+-channel antagonist; and by ryanodine, an inhibitor of Ca2+ release from caffeine- sensitive stores. Depleting intracellular stores with thapsigargin abolished the peak in [Ca2+](i), but the sustained phase was unaffected. Simultaneously measuring membrane potential and [Ca2+](i) indicated that depolarization preceded the rise in [Ca2+](i). These results suggest that ET-1 initiates depolarization in PASMCs, leading to Ca2+ influx through voltage-gated Ca2+ channels and Ca2+ release from ryanodine- inositol 1,4,5-trisphosphate-sensitive stores.

Original languageEnglish (US)
Pages (from-to)L157-L164
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume278
Issue number1 22-1
DOIs
StatePublished - Jan 2000

Keywords

  • Calcium-induced calcium release
  • L-type calcium channels
  • Potassium chloride
  • Vascular smooth muscle

ASJC Scopus subject areas

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

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