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The Journal of Neuroscience, February 1, 2000, 20(3):937-948

Kinetic Differences between Synaptic and Extrasynaptic GABAA Receptors in CA1 Pyramidal Cells

Matthew I. Banks and Robert A. Pearce

Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin 53706

GABAA-mediated IPSCs typically decay more rapidly than receptors in excised patches in response to brief pulses of applied GABA. We have investigated the source of this discrepancy in CA1 pyramidal neurons. IPSCs in these cells decayed rapidly, with a weighted time constant tau Decay of ~18 msec (24°C), whereas excised and nucleated patch responses to brief pulses of GABA (2 msec, 1 mM) decayed more than three times as slowly (tau Decay, ~63 msec). This discrepancy was not caused by differences between synaptic and exogenous transmitter transients because (1) there was no dependence of tau Decay on pulse duration for pulses of 0.6-4 msec, (2) responses to GABA at concentrations as low as 10 µM were still slower to decay (tau Decay, ~41 msec) than IPSCs, and (3) responses of excised patches to synaptically released GABA had decay times similar to brief pulse responses. These data indicate that the receptors mediating synaptic versus brief pulse responses have different intrinsic properties. However, synaptic receptors were not altered by the patch excision process, because fast, spontaneous IPSCs could still be recorded in nucleated patches. Elevated calcium selectively modulated patch responses to GABA pulses, with no effect on IPSCs recorded in nucleated patches, demonstrating the presence of two receptor populations that are differentially regulated by intracellular second messengers. We conclude that two receptor populations with distinct kinetics coexist in CA1 pyramidal cells: slow extrasynaptic receptors that dominate the responses of excised patches to exogenous GABA applications and fast synaptic receptors that generate rapid IPSCs.

Key words: GABAA receptors; hippocampus; receptor kinetics; IPSCs; patch clamp; extrasynaptic receptors

Copyright © 2000 Society for Neuroscience  0270-6474/00/203937-12$05.00/0


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