Modulation of divalent cation-activated chloride ion currents.
1. Voltage-sensitive calcium channel currents carried by Ca2+ (ICa) or Ba2+ (IBa) were followed by tail currents carried by Cl- ions in approximately 45% of cultured dorsal root ganglion neurones. 2. Extracellular application of (-)-baclofen (100 microM) inhibited IBa and ICl(Ba). Bay K 8644 (5 microM) potentiated both currents. 3. Intracellular GTP-gamma-S increased the proportion of neurones in which ICl(Ba) was recorded. In addition, the activation by GTP-gamma-S of a pertussis toxin-sensitive GTP binding (G)-protein resulted in a steady increase in the Cl- tail current with time, despite a concurrent reduction in IBa. 4. Extracellular application of 10mM caffeine selectively reduced ICl(Ba) without significant change in IBa. When Ca2+ was the charge carrier, caffeine had little effect on ICl(Ca), and increased the inactivation of ICa. 5. We conclude that, in addition to being regulated by divalent cation entry through Ca2+ channels, the Cl- current is also regulated by G-protein activation. The mechanism of activation of ICl(Ba) may involve Ca2+ release from intracellular stores.
Scott
R H
RH
Department of Pharmacology, St George's Hospital Medical School, London.
McGuirk
S M
SM
Dolphin
A C
AC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002712:Chlorides / Q000502:physiology*; D005727:Ganglia, Spinal / Q000187:drug effects; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
D015220:Calcium Channels; D002712:Chlorides; D007473:Ion Channels; D013873:Thionucleotides; D001464:Barium; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002110:Caffeine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006160:Guanosine Triphosphate; D001418:Baclofen