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
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.