Influences of external Ca2+ on the GABA-induced chloride current and the efficacy of diazepam in internally perfused frog sensory neurons.
The effects of extracellular Ca2+ on the gamma-aminobutyric acid (GABA)-induced Cl- current and the efficacy of diazepam in the facilitation of GABA response were studied in frog isolated sensory neurons, using a 'concentration clamp' technique which combines a suction pipette (internal perfusion and voltage clamp) and a rapid drug application system. When nominal Ca2+-free external solution was changed to the solution containing 2 mM Ca2+, the response elicited by 1 x 10(-5) M GABA was reduced by about 40% of the control obtained in nominal Ca2+-free solution. The dose-response curve for GABA was shifted to the right without affecting the maximum response. It can be suggested that the application of external Ca2+ modulates the affinity of the GABA receptor to its agonist, GABA. Diazepam at the concentration of 3 x 10(-6) M shifted the dose-response curve for GABA to the left without changing the maximum response with or without external Ca2+. However, the augmentatory action of diazepam on the GABA response was reduced in the presence of external Ca2+. Possible mechanisms for inhibitory action of external Ca2+ on the GABA-gated response and the reduced efficacy of diazepam are discussed.
Akaike
N
N
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Oyama
Y
Y
Yakushiji
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D018118:Chloride Channels; D002712:Chlorides / Q000502:physiology*; D003975:Diazepam / Q000494:pharmacology*; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011892:Rana catesbeiana / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D005680:gamma-Aminobutyric Acid; D003975:Diazepam; D002118:Calcium