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Nitric oxide affects sarcoplasmic calcium release in skeletal myotubes
L M Heunks1, H A Machiels, P N Dekhuijzen
1Department of Pulmonary Diseases, University Hospital Nijmegen, Nijmegen, The Netherlands.
Journal of Applied Physiology (Bethesda, Md. : 1985)
|October 20, 2001
Summary
Nitric oxide (NO) reduces intracellular calcium in mouse skeletal muscle cells. This occurs by affecting the sarcoplasmic reticulum calcium release channel, likely through thiol modification.
Area of Science:
- Muscle physiology
- Cellular signaling
- Biochemistry
Background:
- Skeletal muscle contraction relies on precise calcium (Ca2+) regulation.
- Nitric oxide (NO) is a signaling molecule with diverse cellular roles.
- The sarcoplasmic reticulum (SR) Ca2+-release channel (ryanodine receptor) is critical for muscle excitation-contraction coupling.
Purpose of the Study:
- To investigate the impact of nitric oxide (NO) on intracellular calcium ([Ca2+]i) dynamics in skeletal myotubes.
- To test the hypothesis that NO modulates [Ca2+]i responses by oxidizing thiols on the SR Ca2+-release channel.
Main Methods:
- Real-time confocal microscopy was employed to monitor [Ca2+]i.
- C2C12 mouse skeletal myotubes were stimulated with acetylcholine (ACh) and caffeine.
- The effects of two NO donors, diethylamine NONOate (DEA-NO) and S-nitroso-N-acetyl-penicillamine, were assessed.
Main Results:
- NO donors increased resting [Ca2+]i and dose-dependently reduced ACh-induced [Ca2+]i responses.
- NO donors also diminished the amplitude of caffeine-induced [Ca2+]i responses.
- The effects of DEA-NO were partially reversible with dithiothreitol, suggesting thiol involvement.
Conclusions:
- Nitric oxide (NO) inhibits sarcoplasmic reticulum Ca2+ release in skeletal myotubes.
- This inhibition is likely mediated by the modification of reactive thiols on the ryanodine receptor channel.
- NO plays a regulatory role in skeletal muscle calcium handling.