Contribution of changes in the chloride driving force to the fading of I-GABA in frog melanotrophs

Chloride redistribution during type A gamma-aminobutyric acid (GABA(A)) cur rents (I-GABA) has been investigated in cultured frog pituitary melanotroph s with imposed intracellular chloride concentration ([Cl-](i)) in the whole cell configuration or with unaltered [Cl-](i) using the gramicidin-perfora ted patch approach. Prolonged GABA exposures elicited reproducible decaying currents. The decay of I-GABA was associated with both a transient fall of conductance (g(GABA)) and shift of current reversal potential (E-GABA). Th e shift of E-GABA appeared to be time and driving force dependent. In the g ramicidin-perforated patch configuration, repeated GABA exposures induced c urrents that gradually vanished. The fading of I-GABA was due to persistent shifts of E-GABA as a result of g(GABA) recovering from one GABA applicati on to another. In cells alternatively clamped at potentials closely flankin g resting potential and submitted to a train of brief GABA pulses, a revers al of I-GABA was observed after 150 s recording. It is demonstrated that, i n intact frog melanotrophs, shifts of E-GABA combine with genuine receptor desensitization to depress I-GABA. These findings strongly suggest that shi fts of E-GABA may act as a negative feedback, reducing the bioelectrical an d secretory responses induced by an intense release of GABA in vivo.