Effect of diltiazem on the release of calcium from the canine fragmented cardiac sarcoplasmic reticulum.

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Abstract
Fragmented sarcoplasmic reticulum fraction (SR) was prepared from the ventricle of canine heart, and the effect of diltiazem on its Ca2+ binding and Ca2+ release was examined by centrifugation and filtration methods using 45Ca. Cardiac SR bound 45-55 nmol/mg of Ca2+ in the presence of Mg-ATP. Diltiazem in concentrations up to 10-4 M had little effect on the Ca2+ binding of SR. The membrane of cardiac SR was depolarized by either changing propionate to Cl (anionic) or K to Tris (hydroxymethyl) aminomethane (Tris) (cationic). About 12% of the maximum Ca2+ bound to the SR was released by cationic depolarization, but no Ca2+ was released by anionic depolarization. The Ca2+ release induced by the cationic depolarization was inhibited by diltiazem, and the inhibitory effect of diltiazem on the Ca2+ release was dependent on the incubation time. Incubation of the SR with 3 .times. 10-6 M diltiazem for 30 s almost completely inhibited the Ca2+ release, while incubation with 3 .times. 10-7 M diltiazem incompletely inhibited the Ca2+ release. About 20% of the maximum Ca2+ bound to the SR was released by the addition of 5.1 mM caffeine. The Ca2+ release induced by caffeine was inhibited by increasing the concentration of MgCl2 from 5 to 10 mM, but was not inhibited by 10 mM procaine. An increase of ATP concentration accelerated the time course of the caffeine-induced release of Ca2+ from the SR and subsequent rebinding of Ca2+. Diltiazem up to 10-5 M had no effect on the caffeine-induced Ca2+ release. Diltiazem evidently inhibits the depolarization-induced Ca2+ release from cardiac sarcoplasmic reticulum.