Inhibition of rapid Ca-release from isolated skeletal and cardiac sarcoplasmic reticulum (SR) membranes

Rapid Ca-release from the cisternal compartments isolated from skeletal and cardiac muscle SR was characterized by the use of inhibitors. Ruthenium red (RR) completely blocked (IC50 = 90 nM) the Ca-channels of skeletal SR. Its effect on the rapid Ca-release from cardiac SR was marginal but became optimal (IC50 = 200 nM) in the presence of FLA 365 ([2,6-dichloro-4-dimethyl-aminophenyl] isopropylamine) which by itself had no measurable effect. The antibiotic neomycin mimicked the properties of RR. The strong synergistic effect of RR or neomycin and FLA 365 indicates that either cardiac cisternae contain two distinct isoforms of Ca-release channel, or that different drugs are needed to effectively block the same channel.