Metabolic inhibition with cyanide induces calcium release in pulmonary artery myocytes and Xenopus oocytes

Abstract

We examined the effects of metabolic inhibition on intracellular Ca(2+) release in single pulmonary arterial smooth muscle cells (PASMCs). Severe metabolic inhibition with cyanide (CN, 10 mM) increased intracellular calcium concentration ([Ca(2+)](i)) and activated Ca(2+)-activated Cl(-) currents [I(Cl(Ca))] in PASMCs, responses that were greatly inhibited by BAPTA-AM or caffeine. Mild metabolic inhibition with CN (1 mM) increased spontaneous transient inward currents and Ca(2+) sparks in PASMCs. In Xenopus oocytes, CN also induced Ca(2+) release and activated I(Cl(Ca)), and these responses were inhibited by thapsigargin and cyclopiazonic acid to deplete sarcoplasmic reticulum (SR) Ca(2+), whereas neither heparin nor anti-inositol 1,4,5-trisphosphate receptor (IP(3)R) antibodies affected CN responses. In both PASMCs and oocytes, CN-evoked Ca(2+) release was inhibited by carbonyl cyanide m-chlorophenylhydrazone (CCCP) and oligomycin or CCCP and thapsigargin. Whereas hypoxic stimuli resulted in Ca(2+) release in pulmonary but not mesenteric artery myocytes, CN induced release in both cell types. We conclude that metabolic inhibition with CN increases [Ca(2+)](i) in both pulmonary and systemic artery myocytes by stimulating Ca(2+) release from the SR and mitochondria.