New perspectives in the functional role of GABA(A) channel heterogeneity

Authors
Citation
S. Vicini, New perspectives in the functional role of GABA(A) channel heterogeneity, MOL NEUROB, 19(2), 1999, pp. 97-110
Citations number
79
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR NEUROBIOLOGY
ISSN journal
0893-7648 → ACNP
Volume
19
Issue
2
Year of publication
1999
Pages
97 - 110
Database
ISI
SICI code
0893-7648(199904)19:2<97:NPITFR>2.0.ZU;2-Y
Abstract
gamma-Aminobutyric acid A (GABAA) channels responsible for inhibitory synap tic transmission possess a consistent heterogeneity of structure in terms o f distinct constitutive subunits. During the past 10 years, considerable pr ogress has been made in understanding the magnitude of this large diversity . Structural requirements for clinically important drugs such as benzodiaze pines and barbiturates have been elucidated, and the anatomical distributio n in distinct neuronal populations and the developmental profiles of indivi dual subunits have been elucidated with various techniques. However, the re levance of subunit heterogeneity to synaptic transmission is still largely lacking. Recently, substantial progress has been achieved in understanding the crucial role of desensitization as a molecular determinant in defining the duration and frequency responses of inhibitory synaptic transmission. T his development, together with a combination of different experimental appr oaches, including patch-clamp recordings and ultrafast agonist applications in brain slices and mammalian cells expressing recombinant GABA(A) recepto r, has begun to shed light on a possible role for subunit composition of sy naptic receptors in shaping the physiological characteristics of synaptic t ransmission. Nowhere else in the central nervous system is the anatomical a nd developmental profile of GABA receptor heterogeneity as well understood as it is in the cerebellum. This review summarizes advances in the understa nding of functional correlates to subunit heterogeneity in the cerebellum r elevant for inhibitory synaptic function.