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

Abstract

SUMMARY1. The effects of the Na+ electrochemical potential gradient on y-aminobutyric acid (GABA)-induced C1-currents (ICI) 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 GABAinduced inward ICi was observed under voltage clamp. The reversal potential of GABA-induced Ich (EGABA) was nearly equal to the Cl-equilibrium potential (Ec1), 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 Ic, decreased progressively as VH became more negative. ICi was mediated chiefly by the uptake of GABA subserved by a Na-GABA cotransport mechanism. 7. GABA dose-response measurements were made with and without external Na+.The [Na+]0-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 measure-

Effects of diuretics on GABA‐gated chloride current in frog isolated sensory neurones

“…The results indicate that the decay of the GABA-induced current during GABA application at greater AVVH were the sum of 'true' receptor desensitization and Cl -shifts (Akaike et al, 1987a). We also found in the frog sensory neurones that the GABA-induced Ic, was reduced in the presence of external Na+ and that the inhibition was mediated by the uptake of GABA subserved by a Na-GABA cotransport mechanism (Akaike et al, 1987b). To avoid such contribution of Cl -shifts and GABA uptake in the presence of external Na+ on the kinetic properties of the GABA-gated Icl, therefore, most of recordings of GABA-induced currents were made on neurones perfused with Na+-, K+-and Ca2'-free external and internal solutions containing 120 mM Cl -at AVH less than 20 mV.…”

Axonal GABAA stabilizes excitability in unmyelinated sensory axons secondary to NKCC1 activity

“…We interpret the initial transient component of axonal GABA responses as reflecting partial or complete collapse of the transmembrane chloride gradient. During prolonged GABA application in frog DRG neurons the chloride gradient can fall by 10-15 mV (Akaike et al, 1987) and shifts in E Cl-are likely to be amplified in peripheral axons that have low volumes and are exposed to GABA over a considerable (5-8 mm) length. In addition, GABA A R desensitization which exhibits time constants extending to tens of seconds depending upon the isoform (Bianchi & Macdonald, 2002;Gielen et al, 2012), may also contribute to the transient component of axonal excitability responses to GABA.…”

Inward current caused by sodium‐dependent uptake of GABA in the crayfish stretch receptor neurone.

“…In agreement with these findings, more recent work has shown that manipulations known to inhibit sodium-dependent GABA uptake increase the efficacy of activation of the receptor-gated channels by GABA and those analogues which show the above inactivation or 'fade' phenomenon (Krause et al 1981;Deisz & Dose, 1983; see also Krnjevic, 1984). An increase in the efficacy of GABA action brought about by blocking its uptake has also been observed in various vertebrate preparations (Brown & Scholfield, 1984;Rovira et al 1984;Korn & Dingledine, 1986;Akaike et al 1987).…”