The Journal of Neurophysiology Vol. 77 No. 4 April 1997, pp. 2202-2208
Copyright ©1997 The American Physiological Society

Endogenous GABA Activates Small-Conductance K⁺ Channels Underlying Slow IPSCs in Rat Hippocampal Neurons

Yves De Koninck¹ and Istvan Mody²

¹ Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada; and ² Departments of Neurology and Physiology, UCLA School of Medicine, Los Angeles, California 90095

De Koninck, Yves and Istvan Mody. Endogenous GABA activates small-conductance K⁺ channels underlying slow IPSCs in rat hippocampal neurons. J. Neurophysiol. 77: 2202-2208, 1997. The objective of this study was to determine the properties of K⁺ channels activated by endogenously released trasmitter under synaptic conditions. First, the levels of -aminobutyric acid (GABA) were depleted in hippocampal nerve endings to establish the relative contribution of endogenously released GABA to the activation of GABA_B receptors mediating slow inhibitory postsynaptic currents (IPSCs). Inhibition of glutamic acid decarboxylase and GABA reuptake effectively depleted >85% of the releasable GABA pool, producing parallel reductions of GABA_A and GABA_B receptor-mediated IPSCs, indicating that both classes of receptors are activated synaptically by endogenously released GABA. Whole cell patch-clamp recordings of stimulus-evoked slow IPSCs at potentials hyperpolarized from the potassium reversal potential were consistent with the activation of a nonrectifying (n = 3) or slightly outwardly rectifying (n = 4) K⁺ conductance by the endogenously released GABA. Spectral analysis of the decay phase of GABA_B IPSCs revealed several time constants indicating complex underlying channel kinetics. Nonstationary variance analysis yielded a small unitary conductance in the range of 5-13 pS, consistent with a large number of channels activated during evoked currents. These results indicate that in granule cells of the dentate gyrus, GABA released synaptically from interneuron terminals activates an unusually small K⁺ conductance, with no or slight outward rectification. This conductance is therefore unlike those typically reported for neuronal G protein-coupled K⁺ channels or those activated by exogenously applied baclofen with larger, inwardly rectifying conductances.

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