Muscarinic receptors involved in the subthreshold cholinergic actions of neostriatal spiny neurons.

Abstract

Administration of the peptide MT-1 (48 nM), a selective agonist of muscarinic M(1)-type receptors, mimicked the subthreshold actions of muscarine (1 microM) on neostriatal neurons, i.e., it produced a reduction in subthreshold inward rectification leading to an enhancement in input resistance (R(N)) and evoked discharge. In all recorded cells, MT-1 effects remained in the presence of the specific peptidergic antagonist of the M(4)-type receptor, MT-3 (10 nM), but were blocked by the specific M(1)-type receptor antagonist MT-7 (5 nM). These results suggest that most muscarinic facilitatory actions in the subthreshold voltage range occur through M(1)-type receptors. However, in a fraction of cells (40%) muscarine produced an excitability enhancement not blocked by MT-7. This additional facilitatory action, not present when using MT-1, was blocked by MT-3, suggesting it was mediated by M(4)-type receptor activation. This facilitation could not be blocked by Cs(+), TTX, or Cd(2+), but only by a reduction in extracellular sodium. This result is the first evidence that M(4)-type receptor activation enhances a cationic inward current in a fraction of neostriatal projection neurons.