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J Neurophysiol 86: 2312-2322, 2001;
0022-3077/01 $5.00
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The Journal of Neurophysiology Vol. 86 No. 5 November 2001, pp. 2312-2322
Copyright ©2001 by the American Physiological Society

Kinetic and Pharmacological Properties of GABAA Receptors in Single Thalamic Neurons and GABAA Subunit Expression

S. H. Browne,1,* J. Kang,2,* G. Akk,2 L. W. Chiang,1 H. Schulman,1 J. R. Huguenard,2 and D. A. Prince2

 1Department of Neurobiology and  2Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305-5122

Browne, S. H., J. Kang, G. Akk, L. W. Chiang, H. Schulman, J. R. Huguenard, and D. A. Prince. Kinetic and Pharmacological Properties of GABAA Receptors in Single Thalamic Neurons and GABAA Subunit Expression. J. Neurophysiol. 86: 2312-2322, 2001. Synaptic inhibition in the thalamus plays critical roles in sensory processing and thalamocortical rhythm generation. To determine kinetic, pharmacological, and structural properties of thalamic gamma -aminobutyric acid type A (GABAA) receptors, we used patch-clamp techniques and single-cell reverse transcriptase polymerase chain reaction (RT-PCR) in neurons from two principal rat thalamic nuclei---the reticular nucleus (nRt) and the ventrobasal (VB) complex. Single-channel recordings identified GABAA channels with densities threefold higher in VB than nRt neurons, and with mean open time fourfold longer for nRt than VB [14.6 ± 2.5 vs. 3.8 ± 0.7 (SE) ms, respectively]. GABAA receptors in nRt and VB cells were pharmacologically distinct. Zn2+ (100 µM) reduced GABAA channel activity in VB and nRt by 84 and 24%, respectively. Clonazepam (100 nM) increased inhibitory postsynaptic current (IPSC) decay time constants in nRt (from 44.3 to 77.9 ms, P < 0.01) but not in VB. Single-cell RT-PCR revealed subunit heterogeneity between nRt and VB cells. VB neurons expressed alpha 1-alpha 3, alpha 5, beta 1-3, gamma 2-3, and delta , while nRt cells expressed alpha 3, alpha 5, gamma 2-3, and delta . Both cell types expressed more subunits than needed for a single receptor type, suggesting the possibility of GABAA receptor heterogeneity within individual thalamic neurons. beta  subunits were not detected in nRt cells, which is consistent with very low levels reported in previous in situ hybridization studies but inconsistent with the expected dependence of functional GABAA receptors on beta  subunits. Different single-channel open times likely underlie distinct IPSC decay time constants in VB and nRt cells. While we can make no conclusion regarding beta  subunits, our findings do support alpha  subunits, possibly alpha 1 versus alpha 3, as structural determinants of channel deactivation kinetics and clonazepam sensitivity. As the gamma 2 and delta  subunits previously implicated in Zn2+ sensitivity are both expressed in each cell type, the observed differential Zn2+ actions at VB versus nRt GABAA receptors may involve other subunit differences.

* S. H. Browne and J. Kang contributed equally to this work.




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