TY - JOUR
T1 - Extrasynaptic GABA(A) Receptors
T2 - Form, Pharmacology, and Function
AU - Belelli, Delia
AU - Harrison, Neil L.
AU - Maguire, Jamie
AU - Macdonald, Robert L..
AU - Walker, Matthew C.
AU - Cope, David W.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants GM61925, GM45129, and AA16393 (N.L.H.), MH076994 (J.M.), and NS33300 and NS51590 (R.L.M.); Wellcome Trust Grants WT083163MF (M.C.W.) and 71436 (D.W.C.); Medical Research Council Grant G0400136(M.C.W.);Biotechnology and Biological Research Council Grant C509923, and Case and Strategic Studentships 11426 and 12019 (D.B.); European Union Grant FP6LSHM-CT-2006037315(M.C.W.); Tenovus Scotland(D.B.); A J Clarck Studentship 2007 (D.B.); and Epilepsy Research UK Grants 0404 (M.C.W.) and F0802 (D.W.C.).
Copyright:
© 2009 Society for Neuroscience
PY - 2009/10/14
Y1 - 2009/10/14
N2 - GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABA(A) receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABA(A) receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABA(A) receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.
AB - GABA is the principal inhibitory neurotransmitter in the CNS and acts via GABA(A) and GABA(B) receptors. Recently, a novel form of GABA(A) receptor-mediated inhibition, termed "tonic" inhibition, has been described. Whereas synaptic GABA(A) receptors underlie classical "phasic" GABA(A) receptor-mediated inhibition (inhibitory postsynaptic currents), tonic GABA(A) receptor-mediated inhibition results from the activation of extrasynaptic receptors by low concentrations of ambient GABA. Extrasynaptic GABA(A) receptors are composed of receptor subunits that convey biophysical properties ideally suited to the generation of persistent inhibition and are pharmacologically and functionally distinct from their synaptic counterparts. This mini-symposium review highlights ongoing work examining the properties of recombinant and native extrasynaptic GABA(A) receptors and their preferential targeting by endogenous and clinically relevant agents. In addition, it emphasizes the important role of extrasynaptic GABA(A) receptors in GABAergic inhibition throughout the CNS and identifies them as a major player in both physiological and pathophysiological processes.
KW - CEREBELLAR GRANULE CELLS
KW - AMINOBUTYRIC ACID(A) RECEPTOR
KW - TONIC GABAERGIC INHIBITION
KW - RAT SOMATOSENSORY CORTEX
KW - TEMPORAL-LOBE EPILEPSY
KW - THALAMIC RELAY NEURONS
KW - DELTA-SUBUNIT
KW - NEUROSTEROID MODULATION
KW - DENTATE GYRUS
KW - NEUROACTIVE STEROIDS
U2 - 10.1523/JNEUROSCI.3340-09.2009
DO - 10.1523/JNEUROSCI.3340-09.2009
M3 - Review article
C2 - 19828786
SN - 0270-6474
VL - 29
SP - 12757
EP - 12763
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 41
ER -