Activation and inhibition of the calcium release channel of rabbit skeletal muscle heavy sarcoplasmic reticulum (HSR) was investigated by various methods. The calcium release channel is activated by binding of calcium in the micromolar range and by binding of adenine nucleotides in the millimolar range. Ruthenium red and neomycin are potent inhibitors of the channel at nanomolar to micromolar concentrations. Dantrolene inhibits the rate of caffeine-induced calcium release. Several models of the calcium release channel were considered to explain the three-phasic calcium release from HSR vesicles. Simulation of calcium efflux data according to various models suggest that the calcium release channel has at least three states. The experimental results can be explained by assuming one open and two closed states of the calcium release channel, but not by assuming one open and one closed state.
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