Transmembrane 36Cl- flux measurements and desensitization of the gamma-aminobutyric acidA receptor.

Some data on the concentration range of response and the concentration for half-response (EC50) of gamma-aminobutyric acid (GABA) for the GABAA receptor are reviewed and compared. An analysis of the 36Cl- flux assay demonstrates that both the EC50 and the slope of a Hill plot depend on the ion influx or efflux assay time. The effects of depletion of the 36Cl- concentration gradient during the assay and of receptor desensitization on the result for a range of assay times are considered. The EC50 can be decreased by orders of magnitude by increasing the assay time. The EC50 measured in a finite time is less than the half-response concentration for the response(s) of the receptor. The extent of this difference depends on the receptor concentration per internal volume. The maximal decrease of EC50 depends on the rate of receptor desensitization. The computer simulations showed that a GABAA receptor with a half-response concentration of 100 microM GABA can give 36Cl- flux measurements with an EC50 value 100-fold lower.