M3 muscarinic receptors mediate cholinergic excitation of the spontaneous activity of subthalamic neurons in the rat.
The effect of the muscarinic antagonist on carbachol-induced increase in spontaneous activity of neurons of the subthalamic nucleus was examined by recording the extracellular unitary activity in an in vitro slice preparation. Carbachol produced (98% of the 263 neurons tested) an increase (twofold of the basal at 500 nM) of the discharge frequency. The EC50 for the carbachol-induced effect was 375 +/- 8.7 nM (mean +/- SEM). The response was blocked by muscarinic antagonists in a dose dependent manner. However, the IC50 (94 +/- 3 nM) for the M3 antagonist 4-diphenyl acetoxy-N-methyl piperidine methobromide (4-DAMP) was considerably less than the other muscarinic antagonists (M1 antagonist pirenzepine, IC50 1340 +/- 110 nM; M2 antagonist AF-DX-116, IC50 6780 +/- 690 nM). These results suggest that the cholinergic input to the rat subthalamic nucleus exerts a postsynaptic excitatory action and this effect is likely mediated via muscarinic receptor type 3.
Flores
G
G
Departamento de Fisiologia, Instituto Politecnico Nacional, Mexico.
Hernandez
S
S
Rosales
M G
MG
Sierra
A
A
Martines-Fong
D
D
Flores-Hernandez
J
J
Aceves
J
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013788:Thalamus / Q000187:drug effects*; D013997:Time Factors
D011976:Receptors, Muscarinic; D002217:Carbachol