Abstract
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.
MeSH terms
-
Animals
-
Arginine / analogs & derivatives
-
Arginine / metabolism
-
Arginine / pharmacology
-
Biological Transport / drug effects
-
Caffeine / pharmacology
-
Calcium / metabolism*
-
Calcium Channels / metabolism*
-
Cell Fractionation
-
Electrophysiology
-
Enzyme Inhibitors / pharmacology
-
Lipid Bilayers
-
Muscle Fibers, Fast-Twitch / metabolism
-
Muscle Proteins / metabolism*
-
Muscle, Skeletal / metabolism*
-
NG-Nitroarginine Methyl Ester
-
Nitric Oxide / physiology*
-
Nitric Oxide Synthase / antagonists & inhibitors
-
Nitric Oxide Synthase / metabolism
-
Penicillamine / analogs & derivatives
-
Penicillamine / pharmacology
-
Rabbits
-
Ryanodine Receptor Calcium Release Channel
-
S-Nitroso-N-Acetylpenicillamine
-
Sarcoplasmic Reticulum / metabolism
Substances
-
Calcium Channels
-
Enzyme Inhibitors
-
Lipid Bilayers
-
Muscle Proteins
-
Ryanodine Receptor Calcium Release Channel
-
Nitric Oxide
-
Caffeine
-
S-Nitroso-N-Acetylpenicillamine
-
Arginine
-
Nitric Oxide Synthase
-
Penicillamine
-
Calcium
-
NG-Nitroarginine Methyl Ester