PRESYNAPTIC Γ-Aminobutyric ACID RESPONSES IN THE OLFACTORY CORTEX

100

SUMMARY1. 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 y-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 #M) demonstrated a biphasic membrane voltage change with a later depolarizing phase as a response to higher concentrations (up to 3000 /iM).3. GABA (10-3000 ,uM) 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 ,UM) potently mimicked all the effects of GABA. Bicuculline(1-100 ,/M) 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 JiM) and by strychnine (1 jM). At higher concentrations ( > 10 ,uM), 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 KCI-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 (ro) input capacitance (Cin; representing total membrane capacitance) was calculated as 78-9 * Present address: Laboratoire de Neurobiologie Cellulaire, Centre National de la Recherche Scientifique, Gif-sur-Yvette 91190, France. J. C. R. RANDLE AND L. P. RENAUD ± 2 1 pF. During responses to GABA or muscimol, decreased Rin was accompanied by a linearly related decrease in To indicating that these substances had no effect on the membrane capacitance of s.o.n. neurones.8. These results indicate that the actions of exogenously applied GABA on s.o.n.

Section: Discussionmentioning

confidence: 99%

Actions of gamma‐aminobutyric acid on rat supraoptic nucleus neurosecretory neurones in vitro.

Randle

Renaud

1987

100

“…If the resting membrane conductance is dominated by selectivities for Cl-and K+, then blockage of the Cl-conductance would result in a membrane potential which is highly sensitive to the transmembrane [K+] gradient (Hodgkin & Horowicz, 1959). Such an effect has been described for presynaptic terminals within the cuneate nucleus (Hayes & Simmonds, 1978;Simmonds, 1978) and olfactory cortex (Pickles, 1979). In normal neonatal optic nerves a single supramaximal stimulus generates a relatively large increase of [K+]o which decays with a half-time of about 3 s .…”

Section: Mechanisms Of Cycling Behaviourmentioning

confidence: 99%

Chloride conductance and extracellular potassium concentration interact to modify the excitability of rat optic nerve fibres.

Connors¹,

Ransom²

1984

SUMMARY1. The excitability ofdeveloping rat optic nerves has been studied under conditions in which extracellular Cl-was replaced with other anions.2. In nerves younger than 3 days old, replacing 6. Cycling behaviour is hypothesized to result from a repetition of the following three processes: (i) spontaneous axonal firing elicits a gradual increase in [K+]. which increases axonal excitability and facilitates further K+ release, (ii) axonal firing and K+ release are eventually halted by a combination of depolarization block, intracellular Na+ accumulation and hyperpolarization from electrogenic pumping, (iii) recovery of [K+]. to its minimal value depends on active K+ reuptake mediated by a highly stimulated axonal Na+-K+-ATPase.7. We conclude that a large proportion of the resting membrane conductance of optic nerve fibres is Cl-specific. A high Cl-conductance may stabilize fine central axons against the depolarizing effects of [K+]o increases.

“…In nerve terminals, which are generally far less experimentally accessible, many of the same questions are relevant. Activating GABAA receptors inhibits secretion from nerve terminals in the spinal cord (Nicoll & Alger, 1979;Davidoff & Hackman, 1985;Rudomin, 1990), retina (Tachibana & Kaneko, 1987), olfactory cortex (Pickles, 1979) and posterior pituitary (Dyball & Shaw, 1978;Saridaki, Carter & Lightman, 1989). The depolarization by GABA of dorsal root ganglion cells closely parallels the inhibition of synaptic transmission between primary afferents and spinal neurons (Eccles, 1964), but the precise nature of the connection between primary afferent depolarization and presynaptic inhibition is still unclear (Nicoll & Alger, 1979;Davidoff & Hackman, 1985;Rudomin, 1990).…”

mentioning

confidence: 99%

GABAA receptor activation and the excitability of nerve terminals in the rat posterior pituitary.

Zhang

Jackson

1995

1. The activation of GABAA receptors in nerve terminal membranes gates a Cl-channel.Experiments were conducted to determine how the activation of this receptor influences membrane potentials, action potentials and voltage-activated Na+ and K+ channels.2. When activation of the GABAA receptor produced only conductance changes and no voltage changes, action potentials changed only slightly. The threshold for action potential generation increased by 15%. GABA reduced the broadening of action potentials caused by high frequency stimulation by only 7%. These results indicate that membrane shunting by GABA-gated Cl-channels plays a relatively minor role.3. By recording changes in the current through K+ channels in cell-attached patches, the activation of GABAA receptors was shown to depolarize the nerve terminal membrane from rest by 14 mV. The GABAB receptor agonist baclofen produced no change in resting membrane potential as measured by this same technique. 4. In whole-terminal recordings under current clamp, with pipettes containing various Clconcentrations, the GABA-induced depolarization increased with Ec.. 90 % of the Na+ channels and activated a small amount of K+ current. This suggests that inactivation of Na+ channels makes a major contribution to the inhibition of action potentials by GABA. 8. These results are consistent with the hypothesis that GABA inhibits neurosecretion by retarding impulse propagation into the terminal arborization. These results support a depolarization block mechanism for the inhibition of secretion, in which depolarization inactivates Na+ channels sufficiently to block action potentials.