Drug-induced calcium release from heavy sarcoplasmic reticulum of skeletal muscle

Abstract Calcium release from isolated heavy sarcoplasmic reticulum of rabbit skeletal muscle by several calmodulin antagonistic drugs was measured spectrophotometrically with arsenazo III and compared with the properties of the caffeine-induced calcium release. Trifluoperazine and W7 (about 500 μM) released all actively accumulated calcium (half-maximum release at 129 μM and 98 μM, respectively) in the presence 0.5 mM MgCl 2 and 1 mg/ml sarcoplasmic reticulum protein; calmidazolium (100 μM) and compound 48/80 (70 μg/ml) released maximally 30–40% calcium, whilst bepridil (100 μM) and felodipin (50μM) with calmodulin antagonistic strength similar to trifluoperazine (determined by inhibition of the calcium, calmodulin-dependent protein kinase of cardiac sarcoplasmic reticulum) did not cause a detectable calcium release, indicating that this drug-induced calcium release is not due to the calmodulin antagonistic properties of the tested drugs. Calcium release of trifluoperazine, W7 and compound 48/80 and that of caffeine was inhibited by similar concentrations of magnesium (half-inhibition 1.4–4.2 mM compared with 0.97 mM for caffeine) and ruthenium red (half-inhibition for trifluoperazine, W7 and compound 48/80 was 0.22 μM, 0.08 μM and 0.63 μg/ml, respectively, compared with 0.13 μM for caffeine), suggesting that this drug-induced calcium release occurs via the calcium-gated calcium channel of sarcoplasmic reticulum stimulated by caffeine or channels with similar properties.