Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide

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 are 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.