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1 Center for Cardiovascular Sciences, Albany Medical College, Albany 12208; and 2 Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853
We examined the effects
of metabolic inhibition on intracellular Ca2+ release in
single pulmonary arterial smooth muscle cells (PASMCs). Severe
metabolic inhibition with cyanide (CN, 10 mM) increased intracellular
calcium concentration ([Ca2+]i) and activated
Ca2+-activated Cl
currents
[ICl(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
Ca2+ sparks in PASMCs. In Xenopus oocytes, CN
also induced Ca2+ release and activated
ICl(Ca), and these responses were inhibited by thapsigargin
and cyclopiazonic acid to deplete sarcoplasmic reticulum (SR)
Ca2+, whereas neither heparin nor anti-inositol
1,4,5-trisphosphate receptor (IP3R) antibodies affected CN
responses. In both PASMCs and oocytes, CN-evoked Ca2+
release was inhibited by carbonyl cyanide
m-chlorophenylhydrazone (CCCP) and oligomycin or CCCP and
thapsigargin. Whereas hypoxic stimuli resulted in Ca2+
release in pulmonary but not mesenteric artery myocytes, CN induced release in both cell types. We conclude that metabolic inhibition with
CN increases [Ca2+]i in both pulmonary and
systemic artery myocytes by stimulating Ca2+ release from
the SR and mitochondria.
sarcoplasmic reticulum; mitochondria
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