title: Hyperpolarizing after-potentials regulate generation of long-duration plateau depolarizations in rat paraventricular nucleus neurons.
abstract: 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 PVN neurons tested with 1 microM NMDA agonist (n = 84). The stable plateau phase is characterized by an increase in ionic conductance, from 1.19+/-0.11 nS to 5.24+/-2.17 nS (n = 5). Bath 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 response to NMDA agonist, but long duration plateau depolarizations were not observed. Previous evidence from hypothalamic cultures has demonstrated synaptically driven plateau potentials following the blockade of repolarizing conductances. Pharmacological blockade of the post-spike hyperpolarizing afterpotential with 4-aminopyridine (200 microM), in cells that did not generate plateaux, resulted in the observance of long duration plateau depolarizations in response to a subsequent application of NMDA agonist (n = 4). Our results demonstrate that this 4-aminopyridine-sensitive ionic conductance plays a critical role in determining whether a cell will depolarize for a prolonged duration in response to NMDA receptor activation. As a prolonged depolarization of the postsynaptic membrane and accompanying membrane permeability changes are essential for neurotoxicity, these findings provide evidence for a potential protective mechanism that depends solely on the ability of the cell, through its ionic conductances, to control imposed changes in membrane potential.
authors.affiliation: Department of Physiology, Queen's University, Kingston, ON, Canada.
authors.forename: J S
authors.initials: JS
authors.lastname: Bains
authors.forename: A V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000502:physiology
chemical_list: D015222:Sodium Channels