Effect of the calcium-channel blockers on calcium accumulation in sarcoplasmic reticulum of skeletal muscle.
Vesicular fragments of sarcoplasmic reticulum isolated from rabbit skeletal muscle were actively loaded with Ca2+ in the presence of ATP and an ATP-regenerating system using Arsenazo III as metallochromic indicator to monitor Ca2+ movements across the membrane. Once the Ca2+ release is triggered by the presence of tetraphenylboron in the reaction medium, the addition of verapamil or diltiazem gives rise to a net Ca2+ entry inside the vesicles. Preincubation in the presence of verapamil does not abolish the tetraphenylboron-induced Ca2+ release, the verapamil-induced Ca2+ accumulation being still observed. There appears to be a high-affinity site for verapamil titrated in the micromolar concentration range, whereas diltiazem demonstrates more complex behavior when its concentration is raised. This study suggests the existence of a Ca2+ pathway (putative channels) which is blocked by the drugs tested allowing Ca2+ accumulation inside the vesicles owing to the Ca2+-dependent ATPase activity.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001150:Arsenazo III; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D007473:Ion Channels / Q000378:metabolism; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D013775:Tetraphenylborate / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D001150:Arsenazo III; D013775:Tetraphenylborate; D000255:Adenosine Triphosphate; D014700:Verapamil; D000252:Calcium-Transporting ATPases; D004110:Diltiazem; D002118:Calcium