Ion conductances of isolated sarcoplasmic reticulum (SR) from vertebrate skeletal muscle will be studied to address two types of questions: (1) how are the electrical properties of the SR membrane related to contractile activation in muscle, and (2) what are the basic mechanisms by which the K+ channel of SR operates. Two broad methods will be used: the fusion of isolated SR vesicles into planar phospholipid bilayer membranes, followed by electrical measurement of ionic currents through single channels, and the direct observation of rapid fluxes of ions into SR vesicles via a stopped-flow fluorescence quenching method with millisecond time resolution. K+ channel properties in planar bilayers will be examined in detail, in particular those giving indications of multiple ion interactions within the channel protein. In addition, the SR conductances for anions will be characterized. Specific inhibitors of SR conductances will be sought, both by snythesizing blocker compounds and by searching for endogenous regulators in muscle.