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.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Chloromethyl Ketones / pharmacology
-
Animals
-
Apoptosis* / drug effects
-
Benzopyrans / pharmacology
-
Calcium / metabolism
-
Cerebral Cortex / cytology
-
Cromakalim
-
Cycloheximide / pharmacology
-
Cysteine Proteinase Inhibitors / pharmacology
-
Gadolinium / pharmacology
-
Mice
-
N-Methylaspartate / pharmacology
-
Neurons / cytology*
-
Neurons / metabolism
-
Neuroprotective Agents / pharmacology
-
Nifedipine / pharmacology
-
Patch-Clamp Techniques
-
Potassium / metabolism*
-
Potassium Channels / drug effects
-
Potassium Channels / metabolism*
-
Pyrroles / pharmacology
-
Staurosporine / pharmacology
-
Tetraethylammonium
-
Tetraethylammonium Compounds / pharmacology
-
Veratridine / pharmacology
Substances
-
Amino Acid Chloromethyl Ketones
-
Benzopyrans
-
Cysteine Proteinase Inhibitors
-
Neuroprotective Agents
-
Potassium Channels
-
Pyrroles
-
Tetraethylammonium Compounds
-
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
-
Cromakalim
-
N-Methylaspartate
-
Tetraethylammonium
-
Veratridine
-
Cycloheximide
-
Gadolinium
-
Staurosporine
-
Nifedipine
-
Potassium
-
Calcium