Effect of calcium antagonist drugs on calcium currents in mammalian skeletal muscle fibers.
The calcium channel-inhibiting drugs diltiazem, verapamil and nitrendipine represent three general classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents (ICa++) in rabbit sternomastoid muscle fibers was examined. ICa++ were recorded at room temperature using a vaseline gap voltage clamp. ICa++ measured had similar kinetics to those reported in rat skeletal muscle, were partially blocked by 0.5 mM CdCI2 and could be reduced by substitution of Mg++ for Ca++. Diltiazem reversibly blocked ICa++ in a concentration-dependent manner with the 50% inhibitory concentration (IC50) being 63 microM. Verapamil was slightly more potent with approximately 50% block of ICa++ occurring at 10 microM. In contrast, nitrendipine at concentrations from 1 to 10 microM had no blocking action on ICa++, even after 20 min of exposure. Thus, although Ca++ channels in mammalian skeletal muscle fibers are readily blocked by cadmium, diltiazem and verapamil, these channels appear to be insensitive to the dihydropyridine compound nitrendipine.
K B
KB
Walsh
S H
SH
Bryant
A
A
Schwartz
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009568:Nitrendipine; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007473:Ion Channels; D009568:Nitrendipine; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium