ACTIVATION AND DEACTIVATION RATES OF RECOMBINANT GABA(A) RECEPTOR CHANNELS ARE DEPENDENT ON ALPHA-SUBUNIT ISOFORM

Citation
Am. Lavoie et al., ACTIVATION AND DEACTIVATION RATES OF RECOMBINANT GABA(A) RECEPTOR CHANNELS ARE DEPENDENT ON ALPHA-SUBUNIT ISOFORM, Biophysical journal, 73(5), 1997, pp. 2518-2526
Citations number
43
Categorie Soggetti
Biophysics
Journal title
ISSN journal
00063495
Volume
73
Issue
5
Year of publication
1997
Pages
2518 - 2526
Database
ISI
SICI code
0006-3495(1997)73:5<2518:AADROR>2.0.ZU;2-D
Abstract
The role of subunit composition in determining intrinsic maximum activ ation and deactivation kinetics of GABA(A) receptor channels is unknow n. We used rapid ligand application (100-mu s solution exchange) to ex amine the effects of alpha-subunit composition on GABA-evoked activati on and deactivation rates. HEK 293 cells were transfected with human c DNAs encoding alpha(1) beta(1) gamma(2)- or alpha(2) beta(1) gamma(2)- subunits. Channel kinetics were similar across different transfections of the same subunits and reproducible across several GABA application s in the same patch. Current rise to peak was at least twice as fast f or alpha(2) beta(1) gamma(2) receptors than for alpha(1) beta(1) gamma (2) receptors (reflected in 10-90% rise times of 0.5 versus 1.0 ms, re spectively), and deactivation was six to seven times slower (long time constants of 208 ms versus 31 ms) after saturating GABA applications. Thus alpha-subunit composition determined activation and deactivation kinetics of GABA(A) receptor channels and is therefore likely to infl uence the kinetics and efficacy of inhibitory postsynaptic currents.