Down-regulation of voltage-dependent sodium channels initiated by sodium influx in developing neurons

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.15.5907· OSTI ID:6249603

Dargent, B; Couraud, F ^[1]

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1. Centre National de la Recherche Scientifique, Marseille (France)

To address the issue of whether regulatory feedback exists between the electrical activity of a neuron and ion-channel density, the authors investigated the effect of Na{sup +}-channel activators (scorpion {alpha} toxin, batrachotoxin, and veratridine) on the density of Na{sup +} channels in fetal rat brain neurons in vitro. A partial but rapid (t{sub 1/2}, 15 min) disappearance of surface Na{sup +} channels was observed as measured by a decrease in the specific binding of ({sup 3}H)saxitoxin and {sup 125}I-labeled scorpion {beta} toxin and a decrease in specific {sup 22}Na{sup +} uptake. Moreover, the increase in the number of Na{sup +} channels that normally occurs during neuronal maturation in vitro was inhibited by chronic channel activator treatment. The induced disappearance of Na{sup +} channels was abolished by tetrodotoxin, was found to be dependent on the external Na{sup +} concentration, and was prevented when either choline (a nonpermeant ion) or Li{sup +} (a permeant ion) was substituted for Na{sup +}. Amphotericin B, a Na{sup +} ionophore, and monensin were able to mimick the effect of Na{sup +}-channel activators, while a KCl depolarization failed to do this. This feedback regulation seems to be a neuronal property since Na{sup +}-channel density in cultured astrocytes was not affected by channel activator treatment or by amphotericin B. The present evidence suggests that an increase in intracellular Na{sup +} concentration, whether elicited by Na{sup +}-channel activators or mediated by a Na{sup +} ionophore, can induce a decrease in surface Na{sup +} channels and therefore is involved in down-regulation of Na{sup +}-channel density in fetal rat brain neurons in vitro.

• OSTI ID: 6249603
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 87:15; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
MEMBRANE TRANSPORT
BIOCHEMICAL REACTION KINETICS
SODIUM 22
UPTAKE
TOXINS
RADIORECEPTOR ASSAY
BRAIN
FETUSES
IODINE 125
NERVE CELLS
RATS
TRITIUM COMPOUNDS
ALKALI METAL ISOTOPES
ANIMAL CELLS
ANIMALS
ANTIGENS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MATERIALS
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ODD-ODD NUCLEI
ORGANS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SODIUM ISOTOPES
SOMATIC CELLS
TOXIC MATERIALS
TRACER TECHNIQUES
VERTEBRATES
YEARS LIVING RADIOISOTOPES
550201* - Biochemistry- Tracer Techniques