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), Vol. 9
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ANTICONVULSANTS
BIOCHEMICAL REACTION KINETICS
NERVE CELLS
ELECTROPHYSIOLOGY
RECEPTORS
BIOLOGICAL LOCALIZATION
TOXINS
AUTORADIOGRAPHY
BRAIN
HIPPOCAMPUS
IN VITRO
MEMBRANE TRANSPORT
RATS
SODIUM
TRITIUM COMPOUNDS
ALKALI METALS
ANIMAL CELLS
ANIMALS
ANTIGENS
BODY
CENTRAL NERVOUS SYSTEM
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DRUGS
ELEMENTS
KINETICS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PHYSIOLOGY
PROTEINS
REACTION KINETICS
RODENTS
SOMATIC CELLS
TOXIC MATERIALS
VERTEBRATES
550201* - Biochemistry- Tracer Techniques