title: Effect of diltiazem on the release of calcium from the canine fragmented cardiac sarcoplasmic reticulum.
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 nmoles/mg of Ca ions 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 chloride (anionic) or potassium 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 X 10(-6) M diltiazem for 30 sec almost completely inhibited the release of Ca2+, while incubation with 3 X 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.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000032:analysis; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001552:Benzazepines; D002110:Caffeine; D000252:Calcium-Transporting ATPases; D004110:Diltiazem; D002118:Calcium