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.sub.K]) current and loss of total intracellular [K.sup.+]. This [I.sub.K] augmentation was not seen in neurons undergoing excitotoxic necrosis or in older neurons resistant to staurosporine-induced apoptosis. Attenuating outward [K.sup.+] current with tetraethylammonium or elevated extracellular [K.sup.+], but not blockers of [Ca.sup.2+], [CI.sup.-], or other [K.sup.+] channels, reduced apoptosis, even if associated increases in intracellular [Ca.sup.2+] concentration were prevented. Furthermore, exposure to the [K.sup.+] ionophore valinomycin or the [K.sup.+]-channel opener cromakalim induced apoptosis. Enhanced [K.sup.+] efflux may mediate certain forms of neuronal apoptosis.
Neurons undergo apoptosis during normal development and in certain disease states(1). Elevated extracellular [K.sup.+] interdicts this death(2, 3), an effect attributed to increasing [Ca.sup.2+] influx through voltage-gated [Ca.sup.2+] channels, thus [...]