Sodium channel internalization in developing neurons.
Neurotoxin-induced activation of voltage-dependent Na+ channels provoked rapid (t1/2 = 15-20 min) channel down-regulation in cultured rat brain neurons, resulting in a 50%-70% decrease in [3H]saxitoxin and 125I-alpha-scorpion toxin binding capacities as well as a decrease in Na+ peak current. Experiments using 125I-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.
Dargent
B
B
INSERM U 374, Institut Jean Roche, Faculté de Médecine-Secteur Nord, Marseille, France.
Paillart
C
C
Carlier
E
E
Alcaraz
G
G
Martin-Eauclaire
M F
MF
Couraud
F
F
D000375:Aging / Q000378:metabolism; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000196:embryology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D012530:Saxitoxin / Q000378:metabolism; D012604:Scorpion Venoms / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D012604:Scorpion Venoms; D015222:Sodium Channels; D012530:Saxitoxin; D013779:Tetrodotoxin; D000666:Amphotericin B