Characterization of the binding of the Ptychodiscus brevis neurotoxin T17 to sodium channels in rat brain synaptosomes

Thesis/Dissertation · Tue Jan 01 00:00:00 EST 1985

OSTI ID:6709604

Poli, M A

The lipid-soluble polyether neurotoxins isolated from the marine dinoflagellate Ptychodiscus brevis (formerly Gymnodinium breve) have been determined to bind to a unique receptor site associated with the voltage-sensitive sodium channel in rat brain synaptosomes. Reduction of the C/sub 42/ aldehyde function of T34 to the alcohol function of T17 using NaB/sup 3/H/sub 4/ yielded /sup 3/H-T17 with a specific activity of 15 Ci;/mmol. Using this specific probe, binding to sodium channels was measured at 4/sup 0/CC, 22/sup 0/C, and 37/sup 0/C. Rosenthal analysis of the binding data yielded a K/sub d/ of 2.9 nM and B/sub max/ of 6.8 pmoles /sup 3/H-T17 per mg of synaptosomal protein at 4/sup 0/C. Both K/sub d/ and B/sub max/ were found to be temperature dependent. Depolarization of the synaptosomes by osmotic lysis resulted in the loss of 34% of the available receptor sites, with no decrease in binding affinity. Unlabeled T17, T34, and synthetic T17 (reduced T34) were equipotent in their ability to displace /sup 3/H-T17 from its specific receptor site. Competition experiments using natural toxin probes specific for sites I-IV on the voltage-sensitive sodium channel demonstrate that /sup 3/H-T17 does not bind to any of the previously-described neurotoxin receptor sites. A fifth site is proposed.

• Research Organization: Miami Univ., Coral Gables, FL (USA)
• OSTI ID: 6709604
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
SODIUM COMPOUNDS
UPTAKE
TOXINS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
BRAIN
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NERVE TISSUE
RADIORECEPTOR ASSAY
RATS
TRITIUM COMPOUNDS
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ANIMAL TISSUES
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MAMMALS
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TISSUES
TOXIC MATERIALS
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550301* - Cytology- Tracer Techniques