Acetylcholine raises excitability by inhibiting the fast transient potassium current in cultured hippocampal neurons.
The effects of acetylcholine on cultured hippocampal neurons were investigated by using the whole-cell version of the patch-clamp technique. The CA1 region of the hippocampus was excised from brain slices of young rats (12-19 day old), incubated in a papain solution, and dissociated. Neurons were plated on a glial feeder layer. The experiments were conducted mostly on neurons cultured for 2-6 days. Upon depolarization under voltage clamp, these cells exhibited a fast transient outward current (A-current), which was inhibited by 4-aminopyridine (2.5 mM). Acetylcholine (0.1 microM) also inhibited this A-current, as did the muscarinic agonists bethanechol and muscarine. As expected from their inhibition of the A-current, acetylcholine and 4-aminopyridine both increased the amplitude of the action potential and prolonged its duration. We conclude that the inhibition of the A-current constitutes a mechanism by which acetylcholine exerts its excitatory influence on hippocampal neurons.
D015761:4-Aminopyridine; D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects
D000631:Aminopyridines; D011976:Receptors, Muscarinic; D001285:Atropine; D015761:4-Aminopyridine; D000109:Acetylcholine; D011188:Potassium