Metabolic inhibition with cyanide induces calcium release in pulmonary artery myocytes and Xenopus oocytes.
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.
Wang
Yong-Xiao
YX
Center for Cardiovascular Sciences, Albany Medical College, Albany 12208, USA. wangy@mail.amc.edu
Zheng
Yun-Min
YM
Abdullaev
Iskandar
I
Kotlikoff
Michael I
MI
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003486:Cyanides / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014982:Xenopus laevis
D003486:Cyanides; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium