Muscarinic slow excitation and muscarinic inhibition of synaptic transmission in the rat neostriatum.
Intracellular recording from neurones in rat neostriatal slices was used to compare the muscarinic effects of endogenous acetylcholine (ACh) released from cholinergic neostriatal synapses with the action of exogenously applied muscarinic agonists. Repetitive electrical stimulation in the neostriatum evoked a series of fast excitatory post-synaptic potentials (e.p.s.p.s) followed by a short, variable period of input resistance decrease. In the presence of the acetylcholinesterase (AChE) inhibitor, physostigmine, these potentials were followed by a slow e.p.s.p. which lasted about 60 s. Higher stimulus intensities were needed to elicit the slow e.p.s.p. than the fast e.p.s.p. The slow e.p.s.p. could not be observed after a single stimulus. Its amplitude was graded and increased with stimulus strength. The slow e.p.s.p. was blocked by the muscarinic antagonist atropine (10 microM) and by Ba2+ (100 microM). Input resistance increased during the slow e.p.s.p. Depolarization of the cell increased the size of the slow e.p.s.p. and hyperpolarization decreased it. Simultaneously, resting input resistance increased with membrane depolarization and decreased with membrane hyperpolarization. Repetitive intrastriatal stimulation was followed by a hyperpolarization instead of the depolarization at membrane potentials negative to -75 mV. Input resistance increased during this hyperpolarization as it did during the slow e.p.s.p. The slow e.p.s.p. persisted at membrane potentials of -70 to -80 mV if K+ concentration in the saline was reduced from 5 to 2 mM. In 10 mM-K+, the repetitive stimulation was followed by a hyperpolarization even at membrane potentials as low as -60 to -50 mV. Bath perfusion of high concentrations (100 microM) of muscarine or carbachol induced a sustained increase in the input resistance. The muscarinic agonists also reduced the amplitude of intrastriatally evoked fast e.p.s.p.s; however, this effect was transient and compensated by the increase in input resistance. The effects of the muscarinic agonists on input resistance and e.p.s.p. amplitude were antagonized by atropine (10 microM). Sustained decreases of e.p.s.p. amplitude were induced by the bath application of low doses (0.5-10 microM) of muscarine or carbachol. Input resistance was not altered. Atropine (1-10 microM) antagonized this effect. A sustained reduction of fast e.p.s.p. amplitude resulted also from inhibition of AChE by application of physostigmine (1-100 microM). Input resistance and neuronal excitability were not affected by AChE blockade.(ABSTRACT TRUNCATED AT 400 WORDS)
D000109:Acetylcholine / Q000502:physiology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology*; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D010277:Parasympathomimetics; D001285:Atropine; D000109:Acetylcholine; D011188:Potassium