Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors

MG Lacey, P Calabresi and RA North

Vollum Institute, Oregon Health Sciences University, Portland.

Intracellular recordings were made from presumed dopamine-containing neurons in slices of rat mesencephalon. Muscarine (3-100 microM) increased the rate of spontaneous action potentials; it also caused a membrane depolarization and, in voltage-clamp, an inward current. Concentration-effect curves to muscarine were shifted rightwards by pirenzepine (0.03-1 microM) with an estimated KD of 14 nM. The inward current caused by muscarine was voltage-dependent. Between about -50 and (-)-65 mV it was associated with a decrease in membrane conductance, but between -70 and -110 mV it was unaccompanied by any change in membrane conductance. Muscarine was without effect on the action potential afterhyperpolarization, or on a slowly developing inward current evoked by step hyperpolarizations of up to 20 mV from - 45 mV. Muscarinic depolarizations or inward currents were reduced reversibly or abolished by a low calcium (0.25 mM)/high magnesium (10 mM) solution. It is concluded that muscarinic excitation of dopaminergic neurons is mediated by M1-like receptors.

Volume 253, Issue 1, pp. 395-400, 04/01/1990
Copyright © 1990 by American Society for Pharmacology and Experimental Therapeutics

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