MUSCARINIC INHIBITION OF PERSISTENT NA+ CURRENT IN RAT NEOCORTICAL PYRAMIDAL NEURONS

Muscarinic modulation of persistent Na+ current (I-NaP) was studied us ing whole cell recordings from acutely isolated pyramidal cells of rat neocortex. After suppression of Ca2+ and K+ currents, I-NaP was evoke d by slow depolarizing voltage ramps or by long depolarizing voltage s teps. The cholinergic agonist, carbachol, produced an atropine-sensiti ve decrease of I-NaP at all potentials. When applied at a saturating c oncentration (20 mu M), carbachol reduced peak I-NaP by 38% on average . Carbachol did not alter the voltage dependence of I-NaP activation n or did it interfere with the slow inactivation of I-NaP. Our data indi cate 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 s uited to modulate the electrical behavior of neocortical pyramidal cel ls below and near firing threshold.