title: Nitric oxide enhances slow inactivation of voltage-dependent sodium currents in rat nodose neurons.
abstract: Nitric oxide (NO) can alter neuronal excitability by decreasing the current through voltage-sensitive sodium channels. We hypothesized that NO inhibits sodium currents in part by promoting slow inactivation. We performed whole-cell voltage clamp experiments on sensory neurons from the nodose ganglion. The voltage-dependence of inactivation was determined after stepping the neurons to various potentials between -100 and 30 mV for 200 ms (fast inactivation) and 3 min (slow inactivation) prior to depolarization to 10 mV. NO shifted the voltage of half-inactivation for fast and slow inactivation to more hyperpolarized potentials by 7 and 12 mV, respectively. Sodium currents exhibited a more profound closed state and slow inactivation after exposure to NO. These results demonstrate for the fist time that the slow inactivation of sodium currents is subject to modulation. Due to its effects on fast and slow inactivation, NO may cause a prolonged decrease in neuronal excitability.
authors.affiliation: Department of Internal Medicine, University of Iowa and Veterans Affairs, Medical Center, Iowa City, USA. klaus-bielefeldt@uiowa.edu
authors.forename: K
authors.initials: K
authors.lastname: Bielefeldt
authors.forename: C A
authors.initials: CA
authors.lastname: Whiteis
authors.forename: M W
authors.initials: MW
authors.lastname: Chapleau
authors.forename: F M
authors.initials: FM
authors.lastname: Abboud
mesh_terms: D000818:Animals; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009620:Nodose Ganglion / Q000166:cytology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D006834:Hydrazines; D020030:Nitric Oxide Donors; C112653:PAPA NONOate; D015222:Sodium Channels; D009569:Nitric Oxide; D012964:Sodium