L-type Ca2+ channels, resting [Ca2+](i), and ET-1-induced responses in chronically hypoxic pulmonary myocytes

Larissa A. Shimoda, James S.K. Sham, Tenille H. Shimoda, J. T. Sylvester

Research output: Contribution to journalArticlepeer-review

Abstract

In the lung, chronic hypoxia (CH) causes pulmonary arterial smooth muscle cell (PASMC) depolarization, elevated endothelin-1 (ET-1), and vasoconstriction. We determined whether, during CH, depolarization-driven activation of L-type Ca2+ channels contributes to 1) maintenance of resting intracellular Ca2+ concentration ([Ca2+](i)), 2) increased [Ca2+](i) in response to ET-1 (10-8 M), and 3) ET-1-induced contraction. Using indo 1 microfluorescence, we determined that resting [Ca2+](i) in PASMCs from intrapulmonary arteries of rats exposed to 10% O2 for 21 days was 293.9 ± 25.2 nM (vs. 153.6 ± 28.7 nM in normoxia). Resting [Ca2+](i) was decreased after extracellular Ca2+ removal but not with nifedipine (10-6 M), an L-type Ca2+ channel antagonist. After CH, the ET-1-induced increase in [Ca2+](i) was reduced and was abolished after extracellular Ca2+ removal or nifedipine. Removal of extracellular Ca2+ reduced ET-1-induced tension; however, nifedipine had only a slight effect. These data indicate that maintenance of resting [Ca2+](i) in PASMCs from chronically hypoxic rats does not require activation of L-type Ca2+ channels and suggest that ET-1-induced contraction occurs by a mechanism primarily independent of changes in [Ca2+](i).

Original languageEnglish (US)
Pages (from-to)L884-L894
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume279
Issue number5 23-5
DOIs
StatePublished - 2000

Keywords

  • Chronic hypoxia
  • Contraction
  • Endothelin-1
  • Intracellular calcium concentration
  • Pulmonary artery smooth muscle cells
  • Pulmonary hypertension
  • Smooth muscle
  • Voltage-gated calcium channels

ASJC Scopus subject areas

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

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