Intracellular recordings were obtained from thirty-eight rat supraoptic nucleus (s.o.n.) neurosecretory neurones in perfused hypothalamic explants. Changes in membrane potential and conductance were monitored following application of gamma-aminobutyric acid (GABA), and related agonists and antagonists. 2. GABA depressed action potential discharge of all of thirty-five s.o.n. neurones tested and induced either membrane hyperpolarization or depolarization. Neurones that displayed membrane hyperpolarization in response to lower GABA concentrations (30-300 microM) demonstrated a biphasic membrane voltage change with a later depolarizing phase as a response to higher concentrations (up to 3000 microM). 3. GABA (10-3000 microM) induced a prominent concentration-dependent increase in membrane conductance in all neurones. The critical slope for the log-log plot of [GABA] vs. GABA-induced membrane conductance was 1.7, indicating co-operativity in the GABA receptor-induced conductance change. 4. Muscimol (0.3-30 microM) potently mimicked all the effects of GABA. Bicuculline (1-100 microM) antagonized the effects of GABA and muscimol in a competitive manner. 5. Glycine and taurine (1-10 mM) had weak effects, although comparatively similar to those of GABA. These actions were blocked both by bicuculline (100 microM) and by strychnine (1 microM). At higher concentrations (greater than 10 microM), strychnine also antagonized the actions of GABA. 6. In recordings with potassium-acetate-filled micropipettes, the reversal potential of hyperpolarizing membrane voltage responses to GABA was -72.5 +/- 1.5 mV in close agreement (+/- 5 mV) with the reversal potential of inhibitory post-synaptic potentials (i.p.s.p.s) recorded in the same neurones. Depolarizing responses to GABA reversed polarity at -50 +/- 1.6 mV. In recordings with KCl-filled micropipettes, voltage responses to GABA were always depolarizing and reversed near -40.0 +/- 4.3 mV. Similarly, reduction of the concentration of chloride ions in the perfusion medium from 134 to 10.4 mM induced a positive shift of the GABA reversal potential by 40-50 mV. 7. From measurements of input resistance (Rin) and cell time constant (tau O), input capacitance (Cin; representing total membrane capacitance) was calculated as 78.9 +/- 2.1 pF. During responses to GABA or muscimol, decreased Rin was accompanied by a linearly related decrease in tau o indicating that these substances had no effect on the membrane capacitance of s.o.n. neurones.(ABSTRACT TRUNCATED AT 400 WORDS)
