The action of caffeine on inward barium current through voltage-dependent calcium channels in single rabbit ear artery cells.
The effect of caffeine on inward current carried by barium ions through voltage-dependent calcium channels has been investigated in single rabbit ear artery cells using whole-cell voltage-clamp techniques. Caffeine (1-30 mM) caused a rapid and reversible concentration-dependent blockade of barium current and a related compound, 3-isobutyl-1-methylxanthine (IBMX), was a more potent inhibitor of barium current. Caffeine-induced inhibition of barium current showed no voltage- or use-dependence and caffeine did not alter the steady-state inactivation of barium current. The effect of caffeine was not blocked by extracellular or by intracellular ryanodine or inclusion of both 5 mM 1,2-bis(2-aminophenoxy)-ethane N,N,N',N',-tetraacetic acid (BAPTA) and 2 mM ethylene glycol-bis(beta-amino ethyl ether) N,N,N',N',-tetraacetic acid (EGTA) in the intracellular solution. Rolipram and M&B 22984, non-xanthine inhibitors of phosphodiesterase, did not diminish inward barium current. The data indicate that caffeine and IBMX block voltage-operated calcium channels and it is suggested that this is due to a direct interaction of methylxanthines with the calcium channel.
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, UK.
A D
AD
Hughes
S
S
Hering
T B
TB
Bolton
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure; D001464:Barium / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology* / Q000648:ultrastructure; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D004423:Ear / Q000098:blood supply*; D004553:Electric Conductivity / Q000502:physiology; D005260:Female; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011817:Rabbits; D020889:Rolipram; D014970:Xanthines / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D011760:Pyrrolidinones; D014970:Xanthines; D001464:Barium; C008514:methylxanthine; D002110:Caffeine; C011145:zaprinast; D020889:Rolipram; D015056:1-Methyl-3-isobutylxanthine