SODIUM-CHANNEL INTERNALIZATION IN DEVELOPING NEURONS

Neurotoxin-induced activation of voltage-dependent Na+ channels provoked rapid (t(1/2) = 15-20 min) channel down-regulation in cultured rat brain neurons, resulting in a 50%-70% decrease in [H-3]saxitoxin and I-125-alpha-scorpion toxin binding capacities as well as a decrease in Na+ peak current. Experiments using I-125-alpha-scorpion toxin as both a Na+ channel activator and a surface channel probe showed that a fraction of the bound toxin was internalized, since it was not releasable by acidic washing. Internalization was inhibited by tetrodotoxin, abolished in Na+-free medium, and induced by amphotericin B, a Na+ ionophore. Moreover, down-regulation occurred only in immature neuronal tissue, either cultured fetal neurons or postnatal hippocampal slices, but was absent in adult brain. These observations indicate that Na+ channel internalization is triggered by Na+ influx into neurons and may be involved in the control of electrical activity during development.