Caffeine-induced chloride current in dissociated rat hepatocytes.
Current responses to caffeine in single hepatocytes dissociated from adult rat liver were investigated with the conventional whole cell patch-recording configuration. Caffeine produced a sustained inward current (Icaf) with increasing conductance at a holding potential of -40 mV. The reversal potential of Icaf was close to the Cl- equilibrium potential. Icaf was not affected by the internal perfusion of 1,2-bis(2-amino-phenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or Cs+, whereas the Ca(2+)-activated K+ outward current elicited by A-23187 was inhibited by intracellular BAPTA or Cs+. A 1 mM 3-isobutyl-1-methylxanthine (IBMX) was about equipotent to 1 mM caffeine in inducing the current. Icaf was not modulated by the external application of N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide (H-8), a cyclic nucleotide-dependent protein kinase inhibitor, or intracellular perfusion with guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). It was concluded that caffeine induced an increase in membrane Cl- conductance without utilizing the rise of intracellular free Ca2+ or adenosine 3',5'-cyclic monophosphate (cAMP) and without mediating G protein, suggesting the possible existence of caffeine receptor-Cl- channel complexes on liver plasma membrane.
Yamashita
Y
Y
Department of Physiology, Kyushu University Faculty of Medicine, Fukuoka, Japan.
Akaike
N
N
D000818:Animals; D000838:Anions / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D002469:Cell Separation; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar
D000838:Anions; D018118:Chloride Channels; D002712:Chlorides; D002110:Caffeine; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D002118:Calcium