Possible involvement of K⁺‐conductance in the action of γ‐aminobutyric acid in the guinea‐pig hippocampus

Abstract

1 The mechanism underlying the action of y-aminobutyric acid (GABA) in the hippocampus was investigated using guinea-pig brain slices. 2 GABA either superfused or applied directly by microiontophoresis produced a biphasic response in pyramidal cells, comprising hyperpolarizing and depolarizing components. 3 When different concentrations of GABA were applied to the same neurone, the lower concentrations generally produced a hyperpolarization-predominant response, while higher concentrations resulted in a depolarization-predominant response. 4 The depolarizing component of the response to GABA was augmented in a medium containing a low concentration ofCl-, relatively unaffected by a change in external K+ concentration, and blocked by picrotoxin (2 x 10-5 M). The depolarizing response to GABA persisted in a Ca2+-free medium in which the concentration of Na+ was reduced to 13 mM. 5 Combined application of low doses of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response to GABA and produced a relatively pure hyperpolarizing response. The reversal potential of this pharmacologically 'isolated' hyperpolarizing response to GABA was estimated, from the current-voltage relationships, to be about -90 mV and was the same as that of the hyperpolarization induced by baclofen. 6 When the membrane was successively hyperpolarized by inward direct current (d.c.) injections, the reversal point of the 'pharmacologically isolated' hyperpolarizing response to GABA coincided with that of the post-burst hyperpolarization. 7 Low concentrations of Cl-in the bathing medium had no noticeable effect on the hyperpolarizing component of the response to GABA, whereas it markedly increased the amplitude of the depolarizing component.8 These results suggest that the action of GABA in the hippocampus may involve an activation of K+ conductance.

Electrophysiological actions of GABAB agonists and antagonists in rat dorso‐lateral septal neurones in vitro

“…These results are consistent with those previously described by Gallagher et al (1984). A similar hyperpolarizing response has been described in numerous brain areas including the hippocampus, the cerebral cortex, the thalamus and the medulla (Inoue et al, 1985;Howe et al, 1987;Osmanovic & Shefner, 1987;Lacey et al, 1988;Li & Guyenet, 1995). It has also been (n = 4).…”

Activation of Postsynaptic GABABReceptors Modulates the Bursting Pattern and Synaptic Activity of Olfactory Bulb Juxtaglomerular Neurons

“…Since sodium channels were also blocked by TTX in these experiments, we assume that under these conditions, voltage-dependent calcium channels were the only active channels. Therefore by exclusion, our data suggest that the decrease of mEPSCs by baclofen may involve calcium channels, assuming that the potassium channel blockers-in particular, barium-has blocked the inwardly rectifying potassium channels that were activated by GABA B -Rs (Gahwiler and Brown 1985;Inoue et al 1985;Ogata 1990;Rossi et al 2006). Despite the overall inhibitory effect of baclofen on ET cell firing activity, its paradoxical increase of the number of spikes/bursts would lead to facilitation of transmitter release since additional spikes are expected to increase the probability of synaptic release due to an increase in calcium influx in the dendrites (Murphy et al 2005;Zhou et al 2006).…”

“…GABA B -Rs have been implicated in the modulation of inwardly rectifying, barium-sensitive potassium channels (Gahwiler and Brown 1985;Inoue et al 1985;Ogata 1990;Rossi et al 2006). Our results indicate that baclofen induced an outward current and hyperpolarized the membrane potential of ET cells in the presence of blockers of fast synaptic transmission.…”

Contribution of chloride shifts to the fade of gamma‐aminobutyric acid‐gated currents in frog dorsal root ganglion cells.

“…Therefore, a rapid decline of GABA responses during a continuous GABA application could be accounted for by the sum of the 'true' GABA receptor desensitization and the current run-down through EGABA shifts. In a variety of neuronal tissues such as hippocampus (Alger & Nicoll, 1979; Andersen, Dingledine, Gjerstad, Langmoen & Mosfeldt Laursen, 1980;Inoue, Matsuo & Ogata, 1985;Newberry & Nicoll, 1985), olfactory cortex (Pickels, 1979), cuneate nucleus (Simmonds, 1978), cultured central neurones (Barker & Ransom, 1978) and sensory neurones (Higashi & Nishi, 1982), the GABA responses may not only be mediated by Cl-but also by Na+ or K+, as these previous experiments were performed with an unknown intracellular ionic environment and in the presence of external Na+, K+ and Ca2+. To date, there has been no documentation as to how the decay phase of a 'pure' Cl-response to a continuous GABA application is shaped by receptor desensitization on the one hand and by Cl-redistribution on the other.…”