Administration of the peptide MT-1 (48 nM), a selective agonist of muscarinic M-1-type receptors, mimicked the subthreshold actions of muscarine (1 muM) 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 Cd2+, but only by a reduction in extracellular sodium. This result is the first evidence that M4-type receptor activation enhances a cationic inward current in a fraction of neostriatal projection neurons. (C) 2002 Wiley-Liss, Inc.
Última actualización: 19/10/2018