The agonist effect of Bay K 8644 on neuronal calcium channel currents is promoted by G-protein activation.
Voltage-activated Ca2+ channel currents were recorded from cultured rat dorsal root ganglion neurones using the whole cell clamp technique. Inclusion of 500 microM guanosine 5'-O(3-thio)triphosphate (GTP-gamma-S) in the patch pipette solution resulted in inhibition of the transient component of the Ca2+ channel current. The slowly activating, relatively non-activating Ca2+ channel current which remained in the presence of intracellular GTP-gamma-S was potentiated by the 1,4-dihydropyridine Ca2+ channel agonist Bay K 8644 (5 microM). The percentage increase induced by Bay K 8644 was greater in cells with internal GTP-gamma-S than in control cells. Pretreating cells with pertussis toxin resulted in Bay K 8644 inhibiting rather than increasing Ca2+ channel currents. These results support the hypothesis that L-type Ca2+ channel activity underlies the sustained Ca2+ channel currents which are not inhibited by GTP-gamma-S and that Ca2+ channel ligands require activation of a pertussis toxin-sensitive G protein to exert their agonist effects.
Scott
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RH
Department of Pharmacology, St. George's Hospital Medical School, London, U.K.
Dolphin
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D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013873:Thionucleotides / Q000494:pharmacology
D007473:Ion Channels; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins