Caffeine-induced Ca2+ release activates Ca2+ extrusion via Na+-Ca2+ exchanger in cardiac myocytes.
Rapid application of caffeine in fura-2-dialyzed and whole cell-clamped rat and guinea pig ventricular myocytes activated reversibly large intracellular Ca2+ transients that accompanied Na+-dependent transient inward currents. Such transient inward currents had the same time course as the intracellular Ca2+ transient and were suppressed by Ni2+ and removal of extracellular Na+. Because Ca2+ release signals were not altered by addition of Ni2+ or removal of Na+, we concluded that the rise in intracellular Ca2+ concentration was necessary for the activation of the transient inward current. Thus the caffeine-induced transient inward current represents efflux of Ca2+ via the Na+-Ca2+ exchanger.
Callewaert
G
G
Department of Physiology, University of Pennsylvania, Philadelphia 19104.
Cleemann
L
L
Morad
M
M
D000818:Animals; D001572:Benzofurans; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004553:Electric Conductivity; D005456:Fluorescent Dyes; D016257:Fura-2; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger; D013806:Theophylline / Q000494:pharmacology
D001572:Benzofurans; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D002110:Caffeine; D009532:Nickel; D012964:Sodium; D013806:Theophylline; D002118:Calcium; D016257:Fura-2