Inhibition of calcium spikes and transmitter release by gamma-aminobutyric acid in the guinea-pig myenteric plexus.
The effect of gamma-aminobutyric acid (GABA) (1 microM-1 mM) on synaptic transmission in isolated myenteric ganglia of guinea-pig ileum was investigated with intracellular recording techniques. GABA (up to 1 mM) had no effect on the resting membrane potential and membrane conductance of S neurones. GABA reduced the amplitude of the fast excitatory postsynaptic potential e.p.s.p.) without changing the amplitude of the nicotinic response to ionophoretic application of acetylcholine (ACh). This effect was mimicked by baclofen (10-100 microM) and was not blocked by bicuculline (10 microM). The preparation did not become desensitized during prolonged GABA applications. Cholinergic and non-cholinergic slow e.p.s.ps evoked by single or repetitive presynaptic nerve stimulation were reduced in amplitude by GABA. GABA did not depress muscarinic responses to ionophoretic application of ACh. GABA reduced the duration of the action potential in AH neurones in concentrations that did not affect the membrane potential or conductance. The effect was very marked when electrodes were filled with CsCl, and tetrodotoxin was in the superfusing solution. This effect was also mimicked by baclofen, was insensitive to bicuculline and was not reduced with repeated application or GABA. It is concluded that GABA inhibits release of ACh and the transmitter mediating the slow e.p.s.p. This effect may result from inhibition of an inward calcium current.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers; D005071:Evoked Potentials / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D005680:gamma-Aminobutyric Acid