Sodium‐dependent suppression of gamma‐aminobutyric‐acid‐gated chloride currents in internally perfused frog sensory neurones.

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Abstract
1. The effects of the Na+ electrochemical potential gradient on gamma‐aminobutyric acid (GABA)‐induced Cl‐ currents (ICl) in frog sensory neurones were studied, using a suction pipette technique with which internal perfusion can be accomplished under current‐ and voltage‐clamp conditions. 2. Under current clamp, the depolarizing response to GABA decreased in the presence of external Na+. A similar external Na+‐dependent reduction in the GABA‐induced inward ICl was observed under voltage clamp. The reversal potential of GABA‐induced ICl (EGABA) was nearly equal to the Cl‐ equilibrium potential (ECl), irrespective of the presence or absence of external Na+. 3. Varying the Na+ influx by changing the holding membrane potential (VH) altered the GABA response: the GABA‐induced ICl decreased progressively as VH became more negative. 4. The effects of changing the external and internal Na+ concentrations ([Na+]o and [Na+]i) on the GABA‐induced ICl were also studied. Increasing [Na+]o at a constant [Na+]i reduced this current while increasing [Na+]i at a fixed [Na+]o facilitated it. 5. A high temperature coefficient of about 3 was estimated with respect to the percentage reduction in GABA‐induced ICl due to [Na+]o. 6. These results indicate that the [Na+]o‐dependent suppression of GABA‐induced ICl was mediated chiefly by the uptake of GABA subserved by a Na‐GABA co‐transport mechanism. 7. GABA dose‐response measurements were made with and without external Na+. The [Na+]o‐induced suppression was more pronounced in relative amount at lower concentrations and in absolute amount at intermediate concentrations. Analysis of these data indicates, however, that the Na+‐coupled GABA influx kept increasing at GABA concentrations high enough to nearly saturate GABA‐induced ICl, and the same saturating level was observed as in the Na+‐free case. This indicates that the electrogenic co‐transport current was much smaller so that our measurements of GABA‐induced ICl' were contaminated very little. Thus, the present method based on recording of GABA‐induced ICl was legitimate for the analysis of the Na‐GABA co‐transport. 8. By analysing the [Na+]o‐dependent suppression of GABA‐induced ICl, the stoichiometric ratio of the underlying co‐transport was estimated to be one: one Na+ ion per GABA molecule. 9. The ICl induced by GABA agonists such as beta‐alanine, taurine, l‐GABOB (l‐gamma‐amino‐beta‐hydroxybutyric acid) and muscimol was not affected by the amount of external Na+ present, suggesting difference in the affinity between receptor and transport carrier.