Oxygen-induced fetal pulmonary vasodilation is mediated by intracellular calcium activation of KCa channels

Valerie A. Porter, Michael Rhodes, Helen L. Reeve, David N. Cornfield

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

O2 sensing in fetal pulmonary artery smooth muscle is critically important in the successful transition to air breathing at birth. However, the mechanism by which the fetal pulmonary vasculature senses and responds to an acute increase in O2 tension is not known. Isolated fetal pulmonary artery smooth muscle cells were kept in primary culture for 5-14 days in a hypoxic environment (20-30 mmHg). These cells showed a 25.1 ± 1.7% decrease in intracellular calcium in response to an acute increase in O2 tension. Low concentrations of caffeine (0.5 mM) and diltiazem also decreased intracellular calcium. The decrease in intracellular calcium concentration in response to increasing O2 was inhibited by iberiotoxin and ryanodine. Freshly isolated fetal pulmonary artery smooth muscle cells exhibited "spontaneous transient outward currents," indicative of intracellular calcium spark activation of calciumsensitive potassium channels. The frequency of spontaneous transient outward currents increased when O2 tension was increased to normoxic levels. Increasing fetal pulmonary O2 tension in acutely instrumented fetal sheep increased fetal pulmonary blood flow. Ryanodine attenuated O2-induced pulmonary vasodilation. This study demonstrates that fetal pulmonary vascular smooth muscle cells are capable of responding to an acute increase in O2 tension and that this O2 response is mediated by intracellular calcium activation of calcium-sensitive potassium channels.

Original languageEnglish (US)
Pages (from-to)L1379-L1385
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number6 25-6
DOIs
StatePublished - 2001

Keywords

  • Calcium-sensitive potassium channel
  • Smooth muscle cells
  • Spontaneous transient outward current

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