title: Sodium-activated potassium channels are functionally coupled to persistent sodium currents.
abstract: We report a novel coupled system of sodium-activated potassium currents (I(KNa)) and persistent sodium currents (I(NaP)), the components of which are widely distributed throughout the brain. Its existence and importance has not been previously recognized. Although I(KNa) was known to exist in many cell types, the source of Na(+) which activates I(KNa) remained a mystery. We now show in single membrane patches generated from the somas of rat neurons that sodium influx through I(NaP) is sufficient for activation of K(Na) channels, without substantial contribution from the transient sodium current or bulk [Na(+)](i). I(NaP) was found to be active at cell membrane resting potentials, a finding that may explain why I(KNa) can be evoked from negative holding potentials. These results show an unanticipated role for I(NaP) in activating a negative feedback system countering the excitable effects I(NaP); the interrelatedness of I(NaP) and I(KNa) suggests new ways neurons can tune their excitability.
authors.affiliation: Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Travis A
authors.initials: TA
authors.lastname: Hage
authors.forename: Lawrence
authors.initials: L
authors.lastname: Salkoff
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002478:Cells, Cultured; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D007477:Ions / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D002712:Chlorides; D007477:Ions; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002586:Cesium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D014701:Veratridine; D012964:Sodium; C028019:cesium chloride