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

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Abstract
1 The mechanism underlying the action of γ-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 of Cl−, relatively unaffected by a change in external K+ concentration, and blocked by picrotoxin (2 × 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.