Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes

Leo M.A. Heunks, Herwin A. Machiels, P. N.Richard Dekhuijzen, Y. S. Prakash, Gary C. Sieck

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


In the present study, we used real-time confocal microscopy to examine the effects of two nitric oxide (NO) donors on acetyl-choline (ACh; 10 μM)- and caffeine (10 mM)-induced intracellular calcium concentration ([Ca2+]i) responses in C2C12 mouse skeletal myotubes. We hypothesized that NO reduces [Ca2+]i in activated skeletal myotubes through oxidation of thiols associated with the sarcoplasmic reticulum Ca2+-release channel. Exposure to diethylamine NONOate (DEA-NO) reversibly increased resting [Ca2+]i level and resulted in a dose-dependent reduction in the amplitude of ACh-induced [Ca2+]i responses (25 ± 7% reduction with 10 μM DEA-NO and 78 ± 14% reduction with 100 μM DEA-NO). These effects of DEA-NO were partly reversible after subsequent exposure to dithiothreitol (10 mM). Preexposure to DEA-NO (1, 10, and 50 μM) also reduced the amplitude of the caffeine-induced [Ca2+]i response. Similar data were obtained by using the chemically distinct NO donor S-nitroso-N-acetyl-penicillamine (100 μM). These results indicate that NO reduces sarcoplasmic reticulum Ca2+ release in skeletal myotubes, probably by a modification of hyperreactive thiols present on the ryanodine receptor channel.

Original languageEnglish (US)
Pages (from-to)2117-2124
Number of pages8
JournalJournal of applied physiology
Issue number5
StatePublished - 2001


  • CC myotubes
  • Fluorescence
  • Ryanodine receptor

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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