Actions of γ‐aminobutyric acid on neurones of guinea‐pig myenteric plexus

1 The effects of γ‐aminobutyric acid (GABA) applied by ionophoresis, pressure ejection and superfusion to myenteric neurones of the guinea‐pig ileum were investigated by intracellular recording techniques. 2 Ionophoretic or pressure application of GABA (10 pC‐30 nC) caused membrane depolarizations of AH neurones but not S neurones. This depolarization was associated with a conductance increase. It reversed polarity at a membrane potential of — 18 mV when intracellular electrodes contained KCl, and −39 mV when electrodes contained K acetate, citrate or sulphate. 3 The ionophoretic depolarization was antagonized by bicuculline (1–30 μ M ) in an apparently competitive manner. 4 During prolonged or repeated ionophoretic application of GABA, both the depolarization and conductance increase desensitized. 5 Superfusion of GABA (1–100 μ M ) caused a membrane depolarization in AH neurones, associated with an increase in membrane conductance. The increase in conductance was always smaller than that evoked by ionophoresis of GABA. 6 Bicuculline only partially depressed the depolarization induced by superfusion of GABA, particularly slowing its rising phase. β‐ p ‐Chlorophenyl GABA (baclofen) (10 μ M ) caused a depolarization similar to that observed with GABA in the presence of bicuculline. 7 The depolarization induced by baclofen and GABA (in presence of bicuculline) superfusion did not decline during prolonged applications; superfusion of GABA but not baclofen reversibly reduced or eliminated the effects of GABA ionophoresis. 8 It is concluded that GABA has two effects on the membrane of myenteric neurones. The first is a bicuculline‐sensitive, rapidly desensitizing chloride activation: the second is a bicuculline‐insensitive, non‐desensitizing depolarization.