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J Physiol. Mar 1990; 422: 369–380.
PMCID: PMC1190137

Muscarine reduces inwardly rectifying potassium conductance in rat nucleus accumbens neurones.


1. Intracellular recordings were made from neurones in the nucleus accumbens in slices from the rat brain maintained in vitro. 2. Muscarine (1-100 microM) depolarized 101 of 107 neurones; this was associated with an increase in the input resistance. The potential change reversed polarity with conditioning hyperpolarization and the reversal potential was linearly related to the logarithm of the extracellular potassium concentration. 3. The depolarization caused by muscarine was not changed by tetrodotoxin (1 microM) or by a solution that contained lower levels of calcium (0.24 instead of 2.4 mM), higher levels of magnesium (5 instead of 1.2 mM) and cobalt (2 mM). 4. Muscarine caused an inward current and a decrease in slope conductance when applied to neurones voltage clamped near their resting potential (-82 mV). The current caused by muscarine reversed polarity at the potassium equilibrium potential. The current-voltage relation of the neurones between -60 and -120 mV was well fitted by assuming a voltage-independent potassium conductance and an inward rectifier potassium conductance; muscarine reduced predominantly the inward rectifier conductance. 5. Phorbol-12,13-diacetate (3 microM) and 5-hydroxytryptamine mimicked the action of muscarine. The inward currents caused by muscarine or 5-hydroxytryptamine were occluded by the inward current evoked by the phorbol ester. 6. The depolarization caused by muscarine was competitively antagonized by pirenzepine; the dissociation constant of 11 nM suggested involvement of the M1 receptor. 7. It is concluded that muscarine acts at M1 receptors to reduce the membrane potassium conductance and that activation of protein kinase C may be an intermediate step.

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  • ARUNLAKSHANA O, SCHILD HO. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. [PMC free article] [PubMed]
  • Austin MC, Kalivas PW. The effect of cholinergic stimulation in the nucleus accumbens on locomotor behavior. Brain Res. 1988 Feb 16;441(1-2):209–214. [PubMed]
  • Bloom FE, Costa E, Salmoiraghi GC. Anesthesia and the responsiveness of individual neurons of the caudate nucleus of the cat to acetylcholine, norepinephrine and dopamine administered by microelectrophoresis. J Pharmacol Exp Ther. 1965 Nov;150(2):244–252. [PubMed]
  • Bonner TI. The molecular basis of muscarinic receptor diversity. Trends Neurosci. 1989 Apr;12(4):148–151. [PubMed]
  • Cassell JF, McLachlan EM. Muscarinic agonists block five different potassium conductances in guinea-pig sympathetic neurones. Br J Pharmacol. 1987 Jun;91(2):259–261. [PMC free article] [PubMed]
  • Cortés R, Palacios JM. Muscarinic cholinergic receptor subtypes in the rat brain. I. Quantitative autoradiographic studies. Brain Res. 1986 Jan 8;362(2):227–238. [PubMed]
  • Dodt HU, Misgeld U. Muscarinic slow excitation and muscarinic inhibition of synaptic transmission in the rat neostriatum. J Physiol. 1986 Nov;380:593–608. [PMC free article] [PubMed]
  • Doods HN, Mathy MJ, Davidesko D, van Charldorp KJ, de Jonge A, van Zwieten PA. Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2 and M3 receptors. J Pharmacol Exp Ther. 1987 Jul;242(1):257–262. [PubMed]
  • Dutar P, Nicoll RA. Classification of muscarinic responses in hippocampus in terms of receptor subtypes and second-messenger systems: electrophysiological studies in vitro. J Neurosci. 1988 Nov;8(11):4214–4224. [PubMed]
  • Eltz M, Gmelin G, Wess J, Strohmann C, Tacke R, Mutschler E, Lambrecht G. Presynaptic muscarinic receptors mediating inhibition of neurogenic contractions in rabbit vas deferens are of the ganglionic M1-type. Eur J Pharmacol. 1988 Dec 13;158(3):233–242. [PubMed]
  • Feldberg W, Vogt M. Acetylcholine synthesis in different regions of the central nervous system. J Physiol. 1948 Jun 25;107(3):372–381. [PMC free article] [PubMed]
  • Fibiger HC, Lytle LD, Campbell BA. Cholinergic modulation of adrenergic arousal in the developing rat. J Comp Physiol Psychol. 1970 Sep;72(3):384–389. [PubMed]
  • Fisher SK, Klinger PD, Agranoff BW. Muscarinic agonist binding and phospholipid turnover in brain. J Biol Chem. 1983 Jun 25;258(12):7358–7363. [PubMed]
  • Graybiel AM, Baughman RW, Eckenstein F. Cholinergic neuropil of the striatum observes striosomal boundaries. Nature. 1986 Oct 16;323(6089):625–627. [PubMed]
  • HEBB CO, SILVER A. Choline acetylase in the central nervous system of man and some other mammals. J Physiol. 1956 Dec 28;134(3):718–728. [PMC free article] [PubMed]
  • Herkenham M, Edley SM, Stuart J. Cell clusters in the nucleus accumbens of the rat, and the mosaic relationship of opiate receptors, acetylcholinesterase and subcortical afferent terminations. Neuroscience. 1984 Mar;11(3):561–593. [PubMed]
  • Herz A, Zieglgänsberger W. The influence of microelectrophoretically applied biogenic amines, cholinomimetics and procaine on synaptic excitation in the corpus striatum. Int J Neuropharmacol. 1968 May;7(3):221–230. [PubMed]
  • Higashi H, Inanaga K, Nishi S, Uchimura N. Enhancement of dopamine actions on rat nucleus accumbens neurones in vitro after methamphetamine pre-treatment. J Physiol. 1989 Jan;408:587–603. [PMC free article] [PubMed]
  • Jones DL, Mogenson GJ, Wu M. Injections of dopaminergic, cholinergic, serotoninergic and GABAergic drugs into the nucleus accumbens: effects on locomotor activity in the rat. Neuropharmacology. 1981 Jan;20(1):29–37. [PubMed]
  • Kelly PH, Seviour PW, Iversen SD. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res. 1975 Sep 5;94(3):507–522. [PubMed]
  • Krnjević K, Pumain R, Renaud L. The mechanism of excitation by acetylcholine in the cerebral cortex. J Physiol. 1971 May;215(1):247–268. [PMC free article] [PubMed]
  • Lehmann J, Langer SZ. The striatal cholinergic interneuron: synaptic target of dopaminergic terminals? Neuroscience. 1983 Dec;10(4):1105–1120. [PubMed]
  • McGeer PL, McGeer EG, Fibiger HC, Wickson V. Neostriatal choline acetylase and cholinesterase following selective brain lesions. Brain Res. 1971 Dec 10;35(1):308–314. [PubMed]
  • Mesulam MM, Mufson EJ, Levey AI, Wainer BH. Atlas of cholinergic neurons in the forebrain and upper brainstem of the macaque based on monoclonal choline acetyltransferase immunohistochemistry and acetylcholinesterase histochemistry. Neuroscience. 1984 Jul;12(3):669–686. [PubMed]
  • Nastuk MA, Graybiel AM. Autoradiographic localization and biochemical characteristics of M1 and M2 muscarinic binding sites in the striatum of the cat, monkey, and human. J Neurosci. 1988 Mar;8(3):1052–1062. [PubMed]
  • North RA, Uchimura N. 5-Hydroxytryptamine acts at 5-HT2 receptors to decrease potassium conductance in rat nucleus accumbens neurones. J Physiol. 1989 Oct;417:1–12. [PMC free article] [PubMed]
  • Pfaffinger PJ, Leibowitz MD, Subers EM, Nathanson NM, Almers W, Hille B. Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. Neuron. 1988 Aug;1(6):477–484. [PubMed]
  • Stanfield PR, Nakajima Y, Yamaguchi K. Substance P raises neuronal membrane excitability by reducing inward rectification. Nature. 1985 Jun 6;315(6019):498–501. [PubMed]
  • Uchimura N, Higashi H, Nishi S. Hyperpolarizing and depolarizing actions of dopamine via D-1 and D-2 receptors on nucleus accumbens neurons. Brain Res. 1986 Jun 11;375(2):368–372. [PubMed]
  • Weight FF, Votava J. Slow synaptic excitation in sympathetic ganglion cells: evidence for synaptic inactivation of potassium conductance. Science. 1970 Nov 13;170(3959):755–758. [PubMed]
  • Woodruff GN, McCarthy PS, Walker RJ. Studies on the pharmacology of neurones in the nucleus accumbens of the rat. Brain Res. 1976 Oct 15;115(2):233–242. [PubMed]

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