Differential effects of extra- and intracellular anions on GABA-activated currents in bullfrog sensory neurons.
1. Kinetic properties of gamma-aminobutyric acid (GABA)-gated inward and outward anion currents were investigated in the frog sensory neurons perfused internally and externally with various anions with the use of a rapid concentration-jump (termed as 'concentration-clamp') technique. 2. Extracellular Br- [( Br-]o) shifted the dose-response curves of GABA-induced inward anion currents to the left without affecting the maximum values, whereas [Cl-]o, [I-]o, [No3-]o, [HCOO-]o, and [CH3COO-]o altered the rate of desensitization differently without shifting the GABA dose-response curves, indicating that the kinetics of desensitization phase are affected differently by various extracellular anions. 3. [CH3COO-]o suppressed the maximum current of the dose-response curve of the GABA-induced inward ICl without affecting Kd. 4. Both activation and desensitization phases of GABA-induced ICl consisted of fast and slow components, respectively. [Br-]o, [I-]o, and [NO3-]o significantly prolonged the slow desensitization component, whereas both [HCOO-]o and [CH3COO-]o shortened it. The fast desensitization and the fast and slow activation components were also affected by these foreign anions. 5. GABA dose-response curves of inward currents carried by various intracellular anions (Cl-, Br-, NO3-, I-, SCN-, HCOO-, F-, CH3COO-, CH3CH2COO-, BrO3-, and ClO3-) while keeping a constant [Cl-]o had a constant Kd value but different saturating maximum currents. There were no marked differences among their current kinetics except in the case of SCN-, indicating that the current kinetics is not affected by replacing intracellular Cl- [( Cl-]i) with various foreign anions. 6. The configuration and amplitude of GABA-gated outward anion currents at a constant [Cl-]i reflected the extracellular action of individual anions on the anion-binding site of GABA receptor associated with the anion-selective channel. 7. The relative conductances of the various anions, calculated from the maximum peak currents in dose-response curves of the GABA-induced inward anion currents at a constant [Cl-]o, was in the sequence: I- greater than Br- greater than or equal to NO3- greater than ClO3- greater than SCN- greater than or equal to Cl- greater than HCOO- greater than BrO3- greater than CH3COO- greater than F- greater than CH3CH2COO-.(ABSTRACT TRUNCATED AT 400 WORDS)
Akaike
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N
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
Inomata
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N
Yakushiji
T
T
D000818:Animals; D000838:Anions / Q000494:pharmacology*; D001639:Bicarbonates / Q000494:pharmacology; D001965:Bromides; D002712:Chlorides / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007454:Iodides / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009566:Nitrates / Q000494:pharmacology; D011892:Rana catesbeiana / Q000502:physiology*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000838:Anions; D001639:Bicarbonates; D001965:Bromides; D002712:Chlorides; D007454:Iodides; D009566:Nitrates; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid