Muscarinic modulation of calcium dependent plateau potentials in rat neostriatal neurons

Abstract

Intracellular recording from neostriatal neurons in rat brain slices revealed effects of the acetylcholine (ACh) agonist carbachol (Cch, 1-10 mumol/l), of the anticholinesterase physostigmine (10 mumol/l) and of the muscarinic antagonist atropine (10 mumol/l) on plateau potentials elicited in the presence of K-blockers. Plateau potentials elicited in the presence of K-blockers were Ca-dependent, since they persisted in Na-free solution, were resistant to tetrodotoxin (TTX, 3 mumol/l) and blocked by Cd (0.1-0.5 mmol/l). Cch reduced the duration of the plateau potentials and made them more susceptible to fatigue. These effects were antagonized by atropine (1-10 mumol/l), but not by Ba (100-200 mumol/l) or 4-aminopyridine (4-AP, 0.5 mmol/l). Physostigmine (10 mumol/l) had the same atropine-sensitive effects as Cch on the plateau potential. Atropine (10 mumol/l), by itself, prolonged the duration of the plateau potential. High concentrations (100 mumol/l) of Cch did not further reduce the duration of the plateau potential, instead, the duration re-increased with prolonged exposure. The re-increase of the plateau-spike duration was later masked by bursting activity. The opposing effects of low and high concentrations of Cch on the plateau potential duration corresponded to effects of this drug on intrastriatally evoked EPSPs in that low concentrations of Cch reduced the EPSP amplitude, but high concentrations re-increased it after a transient decrease. It is concluded that the muscarinic effect of ACh in the neostriatum is to modulate Ca-influx and that this effect is exerted in a tonic manner.