Endogenous GABA activates small-conductance K+ channels underlying slow IPSCs in rat hippocampal neurons.
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 gamma-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.
De Koninck
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Y
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Mody
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I
D000704:Analysis of Variance; D000818:Animals; D004553:Electric Conductivity; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D015221:Potassium Channels; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid