Abstract
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 [ 3H]saxitoxin and 125I-α-scorpion toxin binding capacities as well as a decrease in Na + peak current. Experiments using 125I-α-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.
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