PROPERTIES OF THE GABA(A) RECEPTOR OF RAT POSTERIOR PITUITARY NERVE-TERMINALS

1. We investigated gamma-aminobutyric acid (GABA) receptors using thin slice patch-clamp techniques in the swellings along axons of posterio r pituitary nerve terminals. 2. Activation of the nerve terminal GABA( A) receptor induced a mean conductance change of 1.5 nS. Normalizing t o area gave a mean conductance density of 0.38 mS/cm(2). 3. Whereas GA BA(A) receptor-mediated responses could be seen in 91% of the nerve te rminals tested, GABA(B) receptor-mediated responses could not be detec ted. The GABA(B) receptor agonist baclofen had no effect on holding cu rrent or on voltage-activated K+ and Ca2+ channels. It is unlikely tha t nerve terminals of the posterior pituitary contain GABA(B) receptors . 4. The channel gated by the nerve terminal GABA(A) receptor exhibite d only a single open conductance level, Only fully open and fully clos ed states were observed. Subconductance states typical of other GABA(A ) receptor channels were not seen in the GABA-gated channels of poster ior pituitary nerve terminals. 5. Both open time and closed time distr ibutions were biexponential, indicating at least two open and two clos ed 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 similar to 9 s for both GABA and muscimol. 7. Zinc ions at concentrations of 100 mu M reduced GABA res ponses by only 22%. This weak sensitivity to zinc, together with a pre vious observation of benzodiazepine sensitivity, suggested that the ne rve terminal GABA(A) receptor possesses a gamma-subunit. 8. Responses mediated by the GABA(A) receptor persist in whole terminal recordings without Mg-ATP in the pipette solution. Thus, in contrast to many othe r GABA(A) receptors, this receptor showed no rundown in the absence of ATP. 9. The GABA(A) receptor channel of posterior pituitary nerve ter minals has many properties in common with GABA(A) receptors of other p reparations. A number of subtle differences between the nerve terminal receptor described here and cell body receptors described elsewhere m ay reflect the presence of receptor protein subunits unique to nerve t erminals.