Site of anticonvulsant action on sodium channels: autoradiographic and electrophysiological studies in rat brain

Journal Article · Fri May 01 00:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.9.3051· OSTI ID:6355456

Worley, P F; Baraban, J M

The anticonvulsants phenytoin and carbamazepine interact allosterically with the batrachotoxin binding site of sodium channels. In the present study, we demonstrate an autoradiographic technique to localize the batrachotoxin binding site on sodium channels in rat brain using (/sup 3/H)batrachotoxinin-A 20-alpha-benzoate (BTX-B). Binding of (/sup 3/H)BTX-B to brain sections is dependent on potentiating allosteric interactions with scorpion venom and is displaced by BTX-B (Kd approximately 200 nM), aconitine, veratridine, and phenytoin with the same rank order of potencies as described in brain synaptosomes. The maximum number of (/sup 3/H)BTX-B binding sites in forebrain sections also agrees with biochemical determinations. Autoradiographic localizations indicate that (/sup 3/H)BTX-B binding sites are not restricted to cell bodies and axons but are present in synaptic zones throughout the brain. For example, a particularly dense concentration of these sites in the substantia nigra is associated with afferent terminals of the striatonigral projection. By contrast, myelinated structures possess much lower densities of binding sites. In addition, we present electrophysiological evidence that synaptic transmission, as opposed to axonal conduction, is preferentially sensitive to the action of aconitine and veratridine. Finally, the synaptic block produced by these sodium channel activators is inhibited by phenytoin and carbamazepine at therapeutic anticonvulsant concentrations.

• Research Organization: Johns Hopkins Univ. School of Medicine, Baltimore, MD
• OSTI ID: 6355456
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 9; ISSN PNASA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALI METALS
ANIMAL CELLS
ANIMALS
ANTICONVULSANTS
ANTIGENS
AUTORADIOGRAPHY
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ELECTROPHYSIOLOGY
ELEMENTS
HIPPOCAMPUS
IN VITRO
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
METALS
NERVE CELLS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PHYSIOLOGY
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SODIUM
SOMATIC CELLS
TOXIC MATERIALS
TOXINS
TRITIUM COMPOUNDS
VERTEBRATES