title: Mediation of neuronal apoptosis by enhancement of outward potassium current.
abstract: Apoptosis of mouse neocortical neurons induced by serum deprivation or by staurosporine was associated with an early enhancement of delayed rectifier (IK) current and loss of total intracellular K+. This IK augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward K+ current with tetraethylammonium or elevated extracellular K+, but not blockers of Ca2+, Cl-, or other K+ channels, reduced apoptosis, even if associated increases in intracellular Ca2+ concentration were prevented. Furthermore, exposure to the K+ ionophore valinomycin or the K+-channel opener cromakalim induced apoptosis. Enhanced K+ efflux may mediate certain forms of neuronal apoptosis.
authors.affiliation: Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Yu
authors.forename: C H
authors.initials: CH
authors.lastname: Yeh
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
authors.forename: B J
authors.initials: BJ
authors.lastname: Gwag
authors.forename: L M
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: Z S
authors.initials: ZS
authors.lastname: Farhangrazi
authors.forename: H S
authors.initials: HS
authors.lastname: Ying
authors.forename: M
authors.initials: M
authors.lastname: Tian
authors.forename: L L
authors.initials: LL
authors.lastname: Dugan
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D019806:Cromakalim; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005682:Gadolinium / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D001578:Benzopyrans; D015853:Cysteine Proteinase Inhibitors; D018696:Neuroprotective Agents; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019806:Cromakalim; D016202:N-Methylaspartate; D019789:Tetraethylammonium; D014701:Veratridine; D003513:Cycloheximide; D005682:Gadolinium; D019311:Staurosporine; D009543:Nifedipine; D011188:Potassium; D002118:Calcium