A STRUCTURAL DETERMINANT OF DESENSITIZATION AND ALLOSTERIC REGULATIONBY PENTOBARBITAL OF THE GABA(A) RECEPTOR

Functional properties of the alpha(1) beta(1) GABA(A) receptor changes in a subunit-specific manner when a threonine residue in the M2 regio n at the 12' position was mutated to glutamine. The rate and extent of desensitization increased in all mutants but the rate of activation w as faster in the beta(1) mutants. A negligible plateau current and abo lition of potentiation by pentobarbitone of the GABA-activated current depended on the Thr 12' Gin mutation being present in the beta(1) sub unit. The Hill coefficient of the peak current response to GABA was re duced to less than one also in a beta(1) subunit-specific manner. It w as concluded that the beta(1) subunit dominated conformational changes activated by GABA.