HYPERPOLARIZING AFTER-POTENTIALS REGULATE GENERATION OF LONG-DURATIONPLATEAU DEPOLARIZATIONS IN RAT PARAVENTRICULAR NUCLEUS NEURONS

Activation of N-methyl-D-aspartate (NMDA) receptors in a population of neurons of the paraventricular nucleus (PVN) results in long-duration plateau depolarizations during which the membrane rapidly depolarizes , reaching a stable plateau near -20 mV. These responses were observed in 29% of the Type II PVM neurons tested with 1 mu M NMDA agonist (n = 84). The stable plateau phase is characterized by an increase in ion ic conductance, from 1.19 +/- 0.11 nS to 5.24 +/- 2.17 nS (n = 5). Bat h application of tetrodotoxin (n = 4) or alternatively inclusion of QX -314 in the pipette solution (n = 3) prevented the generation of these events. The remaining cells tested (n = 56) also depolarized in respo nse to NMDA agonist, but long duration plateau depolarizations were no t observed. Previous evidence from hypothalamic cultures has demonstra ted synaptically driven plateau potentials following the blockade of r epolarizing conductances. Pharmacological blockade of the post-spike h yperpolarizing afterpotential with 4-aminopyridine (200 mu M), in cell s that did not generate plateaux, resulted in the observance of long d uration plateau depolarizations in response to a subsequent applicatio n of NMDA agonist (n = 4). Our results demonstrate that this 4-aminopy ridine-sensitive ionic conductance plays a critical role in determinin g whether a cell will depolarize for a prolonged duration in response to NMDA receptor activation. As a prolonged depolarization of the post synaptic membrane and accompanying membrane permeability changes are e ssential for neurotoxicity, these findings provide evidence for a pote ntial protective mechanism that depends solely on the ability of the c ell, through its ionic conductances, to control imposed changes in mem brane potential.