title: Caffeine-induced block of Na+ current in guinea pig single ventricular cells.
abstract: Effects of caffeine on Na+ current (INa) were investigated in single ventricular cells from guinea pigs using the whole cell clamp method. With a Ca(2+)-containing internal solution (pCa 8.2), 10 mM caffeine blocked INa by 17.5 +/- 4.6% at a -120-mV holding potential. It was accompanied by 3- to 5-mV shifts of the steady-state inactivation curve and time constant-voltage relationship toward hyperpolarization. The inactivation kinetics spontaneously shifted toward hyperpolarization at 0.30 +/- 0.17 mV/min. The spontaneous shift was accompanied by a similar negative shift of the threshold potential, whereas caffeine did not affect it. Caffeine retarded the recovery of INa from inactivation, and a 4-mV positive shift in the recovery potential produced a similar retardation in INa recovery without caffeine. The INa block by caffeine was not influenced by reinforcing the internal buffering capacities using internal solutions containing 40 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or 50 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid or by pretreating the cell with 1 microM ryanodine. Neither pretreatment with isoproterenol or H 7 nor prestimulation of Gs protein by nonhydrolyzable GTP (GTP gamma S) altered the effects of caffeine on INa. It is concluded that caffeine inhibits INa and shifts the inactivation kinetics without being mediated by changes in intracellular ionic composition or intracellular signaling systems. Direct action on the channel proteins may be involved.
authors.affiliation: Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Habuchi
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tsujimura
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D015222:Sodium Channels; D002110:Caffeine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006160:Guanosine Triphosphate; D012964:Sodium; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D002118:Calcium