Muscarinic inhibition of persistent Na+ current in rat neocortical pyramidal neurons

Muscarinic modulation of persistent Na+ current (I-NaP) was studied using whole cell recordings from acutely isolated pyramidal cells of rat neocortex. After suppression of Ca2+ and K+ currents, I-NaP was evoked by slow depolarizing voltage ramps or by long depolarizing voltage steps. The cholinergic agonist, carbachol, produced an atropine-sensitive decrease of I-NaP at all potentials. When applied at a saturating concentration (20 mu M), carbachol reduced peak I-NaP by 38% on average. Carbachol did not alter the voltage dependence of I-NaP activation nor did it interfere with the slow inactivation of I-NaP. Our data indicate that I-NaP can be targeted by the rich cholinergic innervation of the neocortex. Because I-NaP is activated in the subthreshold voltage range, cholinergic inhibition of this current would be particularly suited to modulate the electrical behavior of neocortical pyramidal cells below and near firing threshold.