Mediation of neuronal apoptosis by enhancement of outward potassium current.
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.
Yu
S P
SP
Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yeh
C H
CH
Sensi
S L
SL
Gwag
B J
BJ
Canzoniero
L M
LM
Farhangrazi
Z S
ZS
Ying
H S
HS
Tian
M
M
Dugan
L L
LL
Choi
D W
DW
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
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