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 o f single ryanodine receptor Ca2+ release channels (RSRCs) in planar li pid bilayers, and these effects mere prevented by the NO quencher hemo globin and reversed by 2-mercaptoethanol. Ca2+ release assessed in ske letal muscle homogenates was also reduced by NO that was generated in situ from L-arginine by endogenous, nitro-L-arginine methylester-sensi tive NO-synthase. The effect of NO on the RyRC might explain NO-induce d depression of contractile force in striated muscles and, since both RyRC isoforms and NOS isoenzymes are ubiquitous, may represent a wide- spread feedback mechanism in Ca2+ signaling; i.e. Ca-dependent activat ion of NO production and NO-evoked reduction of Ca2+ release from intr acellular Ca2+ stores.