Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide.
NO donors were found to reduce the rate of Ca2+ release from isolated skeletal muscle sarcoplasmic reticulum (SR) and the open probability of single ryanodine receptor Ca2+ release channels (RyRCs) in planar lipid bilayers, and these effects were prevented by the NO quencher hemoglobin and reversed by 2-mercaptoethanol. Ca2+ release assessed in skeletal muscle homogenates was also reduced by NO that was generated in situ from L-arginine by endogenous, nitro-L-arginine methylester-sensitive NO-synthase. The effect of NO on the RyRC might explain NO-induced depression of contractile force in striated muscles and, since both RyRC isoforms and NOS isoenzymes aer ubiquitous, may represent a wide-spread feedback mechanism in Ca2+ signaling; i.e. Ca-dependent activation of NO production and NO-evoked reduction of Ca2+ release from intracellular Ca2+ stores.
Mészáros
L G
LG
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta, 30912, USA.
Minarovic
I
I
Zahradnikova
A
A
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002458:Cell Fractionation; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008051:Lipid Bilayers; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D019837:Ryanodine Receptor Calcium Release Channel; D026423:S-Nitroso-N-Acetylpenicillamine; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D015220:Calcium Channels; D004791:Enzyme Inhibitors; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D002110:Caffeine; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester