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| Research article summary (published 30 Aug 1998): |
Endogenous ACh enhances striatal NMDA-responses via M1-like muscarinic receptors and PKC activation.
Full Abstract
Cortical glutamatergic fibres and cholinergic inputs arising from large aspiny interneurons converge on striatal spiny neurons and play a major role in the control of motor activity. We have investigated the interaction between excitatory amino acids and acetylcholine (ACh) on striatal spiny neurons by utilizing intracellular recordings, both in current- and in voltage-clamp mode in rat brain slices. Muscarine (0.3-10 microM) produced a reversible and dose-dependent increase in the membrane depolarizations/inward currents induced by brief applications of N-methyl-D-aspartate (NMDA), while it did not affect the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-induced responses. These concentrations of muscarine did not alter the membrane potential and the current-voltage relationship of the recorded cells. Neostigmine (0.3-10 microM), an ACh-esterase inhibitor, mimicked this facilitatory effect. The facilitatory effects of muscarine and neostigmine were antagonized either by scopolamine (3 microM) or by pirenzepine (10-100 nM), an antagonist of M1-like muscarinic receptors, but not by methoctramine (300 nM), an antagonist of M2-like muscarinic receptor. Accordingly, these facilitatory effects were mimicked by McN-A-343 (1-10 microM), an agonist of M1-like muscarinic receptors, but not by oxotremorine (300 nM), an agonist of M2-like receptors. Tetrodotoxin (TTX) did not block the facilitatory effect produced by the activation of muscarinic receptors suggesting that this effect is postsynaptically mediated. The action of neostigmine was prevented either by the intracellular calcium (Ca2+) chelator BAPTA (200 mM) or by preincubating the slices with inhibitors of protein kinase C (PKC) (staurosporine 100 nM or calphostin C 1 microM). McN-A-343 did not alter the excitatory post synaptic potentials (EPSPs) evoked by corticostriatal stimulation in the presence of physiological concentration of magnesium (Mg2+ 1.2 mM), while it enhanced the duration of these EPSPs recorded in the absence of external magnesium. Our data show that endogenous striatal ACh exerts a positive modulatory action on NMDA responses via M1-like muscarinic receptors and PKC activation.
Author information
Author/s: Calabresi, P (P); Centonze, D (D); Gubellini, P (P); Pisani, A (A); Bernardi, G (G);
Affiliation: Clinica Neurologica, Dip. Neuroscienze, Università di Roma Tor Vergata, Rome, Italy. calabre(-atsign-)uniroma2.it
Journal and publication information
Publication Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't
Journal: The European journal of neuroscience (Eur J Neurosci), published in FRANCE. (Language: eng)
Reference: 1998-Sep; vol 10 (issue 9) : pp 2887-95
Dates: Created 1999/06/07; Completed 1999/06/07; Revised 2007/11/15;
PMID: 9758158, status: MEDLINE (last retrieved date: 2/18/2009)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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MeSH headings (categories)
This article was linked to the MeSH Headings (categories) shown below.
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Associated Chemicals: Excitatory Amino Acids (0) ; Receptor, Muscarinic M1 (0) ; Receptor, Muscarinic M2 (0) ; Receptors, Muscarinic (0) ; Muscarine (300-54-9) ; Acetylcholine (51-84-3) ; (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride (55-45-8) ; Neostigmine (59-99-4) ; N-Methylaspartate (6384-92-5) ; Egtazic Acid (67-42-5) ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (77521-29-0) ; 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (85233-19-8) ; Protein Kinase C (EC 2.7.11.13)Related articles
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