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 journalArticleAcademicpeer-review

Abstract

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
Pages (from-to)2117-2124
Number of pages8
JournalJournal of Applied Physiology
Volume91
Issue number5
Publication statusPublished - 10 Nov 2001

Cite this

Heunks, L. M. A., Machiels, H. A., Dekhuijzen, P. N. R., Prakash, Y. S., & Sieck, G. C. (2001). Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes. Journal of Applied Physiology, 91(5), 2117-2124.