Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors.
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.
Lacey
M G
MG
Vollum Institute, Oregon Health Sciences University, Portland.
Calabresi
P
P
North
R A
RA
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000502:physiology
D011976:Receptors, Muscarinic; D009116:Muscarine; D004298:Dopamine