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)) currents (I(GABA)) has been investigated in cultured frog pituitary melanotrophs with imposed intracellular chloride concentration ([Cl(-)](i)) in the whole cell configuration or with unaltered [Cl(-)](i) using the gramicidin-perforated 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)). The shift of E(GABA) appeared to be time and driving force dependent. In the gramicidin-perforated patch configuration, repeated GABA exposures induced currents 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 application to another. In cells alternatively clamped at potentials closely flanking resting potential and submitted to a train of brief GABA pulses, a reversal of I(GABA) was observed after 150 s recording. It is demonstrated that, in intact frog melanotrophs, shifts of E(GABA) combine with genuine receptor desensitization to depress I(GABA). These findings strongly suggest that shifts of E(GABA) may act as a negative feedback, reducing the bioelectrical and secretory responses induced by an intense release of GABA in vivo.
Le Foll
F
F
European Institute for Peptide Research (Institut Fédératif de Recherches Multidisciplinaires sur les Peptides no. 23), Laboratory of Cellular and Molecular Neuroendocrinology, Institut National de la Santé et de la Recherche Médicale Unité, France.
Soriani
O
O
Vaudry
H
H
Cazin
L
L
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D006096:Gramicidin; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism*; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011895:Rana ridibunda; D011963:Receptors, GABA-A / Q000502:physiology*
D002712:Chlorides; D011963:Receptors, GABA-A; D006096:Gramicidin; D009074:Melanocyte-Stimulating Hormones