GABAA receptor‐mediated increase in membrane chloride conductance in rat paratracheal neurones

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Abstract
The actions of γ‐aminobutyric acid (GABA) on the intramural neurones of 14–18 day old rats were studied in situ by use of intracellular current‐ and voltage‐clamp techniques. The ionic conductance changes and the effects of various GABA‐receptor agonists and antagonists on these neurones were also investigated. Prolonged application of GABA either by ionophoresis (10 pC‐10 nC) or superfusion (10–100 μm), evoked a biphasic membrance depolarization in over 90% of all paratracheal neurones studied. Typically, the response consisted of an initial rapid depolarization (18–45 ms) that subsequently faded over a period of 15–25 s to reveal a second smaller depolarization which was maintained for the duration of GABA application. Both components of the evoked response resulted in an increase in membrane conductance and an inward flow of current. The amplitude of the transient inward current, recorded during the initial phase of the response, was linearly related to the membrane potential at which it was elicited and reversed symmetrically at a membrane potential of −32.7 mV. The underlying increase in conductance was largely independent of membrane potential. The equilibrium potential for the sustained inward current was −38.7 mV. Replacement of extracellular chloride with gluconate ions initially enhanced the GABA‐evoked inward current. With successive applications of GABA in low chloride, the evoked current and conductance changes declined markedly. Muscimol superfusion (1–10 μm) or ionophoresis (10 pC‐10 nC) mimicked both the initial and late phases of the GABA‐induced conductance change and inward current. Baclofen (1–100 μm) had no effect upon either resting membrane potential or conductance in any of the cells tested. The large transient initial phase of the GABA‐evoked inward current and depolarization were potently inhibited by picrotoxin (1–50 μm), whereas the smaller sustained inward current was largely resistant to picrotoxin. All of the observed actions of GABA and muscimol were antagonized by bicuculline (0.1–10 μm) in an apparently competitive manner. It is concluded that GABA acts via GABAA receptors present on the soma of paratracheal neurones to produce an increase in membrane chloride conductance. Prolonged application of GABA results in a decline in the observed current due to a combination of two processes: receptor desensitization and shifts in the chloride equilibrium potential. The possible roles for GABA in neural regulation of airway excitability are discussed.