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

Muscarinic modulation of persistent Na+ current (INaP) was studied using whole cell recordings from acutely isolated pyramidal cells of rat neocortex. After suppression of Ca2+ and K+ currents, INaP was evoked by slow depolarizing voltage ramps or by long depolarizing voltage steps. The cholinergic agonist, carbachol, produced an atropine-sensitive decrease of INaP at all potentials. When applied at a saturating concentration (20 microM), carbachol reduced peak INaP by 38% on average. Carbachol did not alter the voltage dependence of INaP activation nor did it interfere with the slow inactivation of INaP. Our data indicate that INaP can be targeted by the rich cholinergic innervation of the neocortex. Because INaP 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.