Alpha-scorpion toxins binding on rat brain and insect sodium channels reveal divergent allosteric modulations by brevetoxin and veratridine. 1995

S Cestèle, and R B Ben Khalifa, and M Pelhate, and H Rochat, and D Gordon
Faculty of Medicine Nord, Institut Féderatif de Recherche Jean Roche, Laboratory of Biochemistry, URA CNRS 1455, Marseille, France.

At least six topologically separated neurotoxin receptor sites have been identified on sodium channels that reveal strong allosteric interactions among them. We have studied the allosteric modulation induced by veratridine, binding to receptor site 2, and brevetoxin PbTx-1, occupying receptor site 5, on the binding of alpha-scorpion toxins at receptor site 3, on three different neuronal sodium channels: rat brain, locust, and cockroach synaptosomes. We used 125I-AaH II, the most active alpha-scorpion toxin on vertebrates, and 125I-Lqh alpha IT, shown to have high activity on insects, as specific probes for receptor site 3 in rat brain and insect sodium channels. Our results reveal that brevetoxin PbTx-1 generates three types of effects at receptor site 3:1) negative allosteric modulation in rat brain sodium channels, 2) positive modulation in locust sodium channels, and 3) no effect on cockroach sodium channel. However, PbTx-1 activates sodium channels in cockroach axon similarly to its activity in other preparation. Veratridine positively modulates both rat brain and locust sodium channels but had no effect on alpha-toxin binding in cockroach. The dramatic differences in allosteric modulations in each sodium channel subtype suggest structural differences in receptor sites for PbTx-1 and/or at the coupling regions with alpha-scorpion toxin receptor sites in the different sodium channels, which can be detected by combined application of specific channel modifiers and may elucidate the dynamic gating activity and the mechanism of allosteric interactions among various neurotoxin receptors.

UI MeSH Term Description Entries
D007457 Iodine Radioisotopes Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Radioisotopes, Iodine
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008387 Marine Toxins Toxic or poisonous substances elaborated by marine flora or fauna. They include also specific, characterized poisons or toxins for which there is no more specific heading, like those from poisonous FISHES. Marine Biotoxins,Phycotoxins
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009498 Neurotoxins Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D010526 Periplaneta A genus in the family Blattidae containing several species, the most common being P. americana, the American cockroach. Periplaneta americana,American Cockroach,American Cockroaches,American Cockroache,American Cockroachs,Cockroach, American,Cockroache, American,Cockroaches, American,Cockroachs, American,Periplaneta americanas,Periplanetas,americana, Periplaneta
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D006110 Grasshoppers Plant-eating orthopterans having hindlegs adapted for jumping. There are two main families: Acrididae and Romaleidae. Some of the more common genera are: Melanoplus, the most common grasshopper; Conocephalus, the eastern meadow grasshopper; and Pterophylla, the true katydid. Acrididae,Locusts,Romaleidae,Grasshopper,Locust
D000494 Allosteric Regulation The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES. Regulation, Allosteric,Allosteric Regulations,Regulations, Allosteric
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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