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Single-channel properties of synaptic and extrasynaptic GABA(A) receptors suggest differential targeting of receptor subtypes

Brickley, SG; Cull-Candy, SG; Farrant, M; (1999) Single-channel properties of synaptic and extrasynaptic GABA(A) receptors suggest differential targeting of receptor subtypes. J NEUROSCI , 19 (8) 2960 - 2973.

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Abstract

Many neurons express a multiplicity of GABA(A) receptor subunit isoforms. Despite having only a single source of inhibitory input, the cerebellar granule cell displays, at various stages of development, more than 10 different GABA(A) subunit types. This subunit diversity would be expected to result in significant receptor heterogeneity, yet the functional consequences of such heterogeneity remain poorly understood. Here we have used single-channel properties to characterize GABA(A) receptor types in the synaptic and extrasynaptic membrane of granule cells. In the presence of high concentrations of GABA, which induced receptor desensitization, extrasynaptic receptors in outside-out patches from the soma entered long-lived closed states interrupted by infrequent clusters of openings. Each cluster of openings, which is assumed to result from the repeated activation of a single channel, was to one of three main conductance states (28, 17, or 12 pS), the relative frequency of which differed between patches. Such behavior indicates the presence of at least three different receptor types. This heterogeneity was not replicated by individual recombinant receptors (alpha(1)beta(2)gamma(2S) or alpha(1)beta(3)gamma(2S)), which gave rise to clusters of a single type only. By contrast, the conductance of synaptic receptors, determined by fluctuation analysis of the synaptic current or direct resolution of channel events, was remarkably uniform and similar to the highest conductance value seen in extrasynaptic patches. These results suggest that granule cells express multiple GABA(A) receptor types, but only those with a high conductance, most likely containing a gamma subunit, are activated at the synapse.

Type: Article
Title: Single-channel properties of synaptic and extrasynaptic GABA(A) receptors suggest differential targeting of receptor subtypes
Keywords: cerebellar granule cell, GABA(A) receptor, synaptic, single channel, subunit heterogeneity, differential targeting, CEREBELLAR GRANULE CELLS, SUBUNIT MESSENGER-RNAS, A RECEPTORS, RAT-BRAIN, GABA(A)-RECEPTOR SUBTYPES, DEVELOPMENTAL-CHANGES, GAMMA-2 SUBUNIT, OLFACTORY-BULB, BETA SUBUNITS, ION CHANNELS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/92528
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