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 (I-K) current and loss of total intracellular K+. This I-K a ugmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenu ating outward K+ current with tetraethylammonium or elevated extracell ular K+, but not blockers of Ca2+, Cl-, or other K+ channels, reduced apoptosis, even if associated increases in intracellular Ca2+ concentr ation were prevented. Furthermore, exposure to the K+ ionophore valino mycin or the K+-channel opener cromakalim induced apoptosis. Enhanced K+ efflux may mediate certain forms of neuronal apoptosis.