Properties of the GABAA receptor of rat posterior pituitary nerve terminals.

Abstract

1. We investigated gamma-aminobutyric acid (GABA) receptors using thin slice patch-clamp techniques in the swellings along axons of posterior pituitary nerve terminals. 2. Activation of the nerve terminal GABAA receptor induced a mean conductance change of 1.5 nS. Normalizing to area gave a mean conductance density of 0.38 mS/cm2. 3. Whereas GABAA receptor-mediated responses could be seen in 91% of the nerve terminals tested, GABAB receptor-mediated responses could not be detected. The GABAB receptor agonist baclofen had no effect on holding current or on voltage-activated K+ and Ca2+ channels. It is unlikely that nerve terminals of the posterior pituitary contain GABAB receptors. 4. The channel gated by the nerve terminal GABAA receptor exhibited only a single open conductance level. Only fully open and fully closed states were observed. Subconductance states typical of other GABAA receptor channels were not seen in the GABA-gated channels of posterior pituitary nerve terminals. 5. Both open time and closed time distributions were biexponential, indicating at least two open and two closed conformations of the channel. At a higher GABA concentration, long-duration openings predominated, suggesting that long-duration openings were distinguished from short-duration openings by the occupation of a greater number of agonist binding sites. 6. Sustained application of GABA desensitized the receptor with simple exponential kinetics. The time constant for desensitization was approximately 9 s for both GABA and muscimol. 7. Zinc ions at concentrations of 100 microM reduced GABA responses by only 22%. This weak sensitivity to zinc, together with a previous observation of benzodiazepine sensitivity, suggested that the nerve terminal GABAA receptor possesses a gamma-subunit. 8. Responses mediated by the GABAA receptor persist in whole terminal recordings without Mg-ATP in the pipette solution. Thus, in contrast to many other GABAA receptors, this receptor showed no rundown in the absence of ATP. 9. The GABAA receptor channel of posterior pituitary nerve terminals has many properties in common with GABAA receptors of other preparations. A number of subtle differences between the nerve terminal receptor described here and cell body receptors described elsewhere may reflect the presence of receptor protein subunits unique to nerve terminals.