Multiple effects of caffeine on calcium current in rat ventricular myocytes.
Caffeine exerts a number of different effects on L-type calcium current in rat ventricular myocytes. These include: (1) a slowing of inactivation that is comparable to, but not additive to, that produced by prior treatment of the cells with ryanodine (a selective sarcoplasmic reticulum Ca2+ releaser) or high concentrations of intracellular 1,2-bis[2-aminophenoxy]ethane-N,N,N',-N'-tetraacetic acid (BAPTA) (a fast Ca2+ chelator), (2) a stimulation of peak ICa that is comparable to, but not additive to that produced by prior treatment with isobutylmethylxanthine (a selective phosphodiesterase inhibitor), and (3) a dose-dependent decrease of peak ICa that is not prevented by pretreatment with any of these agents. None of the caffeine actions could be mimicked or prevented by administration of 8-phenyltheophylline, a specific adenosine receptor antagonist. We conclude that only the slowing of ICa inactivation is due to caffeine's ability to deplete the sarcoplasmic reticulum of calcium. The stimulatory effect of caffeine on peak ICa is probably due to phosphodiesterase inhibition, while caffeine's inhibitory effect on ICa is independent of these processes and could be a direct effect on the channel. The multiplicity of caffeine actions independent of its effects on the sarcoplasmic reticulum lead to the conclusion that ryanodine, though slower acting and essentially irreversible, is a more selective agent than caffeine for probing sarcoplasmic reticulum function and its effects on other processes.
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Institute of Molecular Physiology and Genetics, Slovak Academy of Science, Bratislava.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D015220:Calcium Channels; D018047:Receptors, Purinergic P1; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D013806:Theophylline; C028322:8-phenyltheophylline; D010727:Phosphoric Diester Hydrolases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D015056:1-Methyl-3-isobutylxanthine