Modulation of Ca(2+)-stimulated glutamate release from synaptosomes by Na+ entry through tetrodotoxin-sensitive channels. 1994

M A Romano-Silva, and M V Gomez, and M J Brammer
Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Tityustoxin (TsTX), a toxin obtained from the venom of the Brazilian scorpion Tityus serrulatus, stimulates Na+ influx through tetrodotoxin (TTX)-sensitive Na+ channels which, in turn, promotes both Ca(2+)-dependent and Ca(2+)-independent release of glutamate from rat cerebrocortical synaptosomes. The level of Ca(2+)-dependent glutamate release after addition of 0.5 microM TsTX is greater than that produced by a maximally depolarizing concentration of KCl. This effect of TsTX, which is entirely dependent on Na+ entry, suggests that Na+ has a role in modulating Ca2+ entry and glutamate release that is not simply related to membrane depolarization. In order to investigate possible modulatory role(s) of Na+ on Ca(2+)-dependent glutamate release, we compared the effects of TsTX with those of KCl and the Na+ ionophore gramicidin D. When used alone, 100 nM gramicidin D produced a larger increase in intrasynaptosomal free Na+ than did 0.5 microM TsTX, and a similar rise in intrasynaptosomal free Ca2+, but was much less effective in promoting glutamate release. Even the combination of membrane depolarization (by 33 mM KCl) and elevation of intrasynaptosomal free Na+ (by 100 nM gramicidin) was still less effective than TsTX at causing Ca(2+)-dependent glutamate release. These data suggest that localized Na+ entry, through TTX-sensitive Na+ channels, exerts a modulatory role on Ca(2+)-dependent glutamate release from nerve endings in the cerebral cortex.

UI MeSH Term Description Entries
D008297 Male Males
D011189 Potassium Chloride A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA. Slow-K,Chloride, Potassium
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D006096 Gramicidin A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN. Gramicidin A,Gramicidin A(1),Gramicidin B,Gramicidin C,Gramicidin D,Gramicidin Dubos,Gramicidin J,Gramicidin K,Gramicidin NF,Gramicidin P,Gramicidin S,Gramicidins,Gramoderm,Linear Gramicidin,Gramicidin, Linear
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
D012604 Scorpion Venoms Venoms from animals of the order Scorpionida of the class Arachnida. They contain neuro- and hemotoxins, enzymes, and various other factors that may release acetylcholine and catecholamines from nerve endings. Of the several protein toxins that have been characterized, most are immunogenic. Scorpion Toxin,Scorpion Toxins,Scorpion Venom Peptide,Tityus serrulatus Venom,Scorpion Venom,alpha-Scorpion Toxin,beta-Scorpion Toxin,gamma-Scorpion Toxin,Peptide, Scorpion Venom,Toxin, Scorpion,Toxin, alpha-Scorpion,Toxin, beta-Scorpion,Venom Peptide, Scorpion,Venom, Scorpion,Venom, Tityus serrulatus,alpha Scorpion Toxin,beta Scorpion Toxin,gamma Scorpion Toxin
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D013574 Synaptosomes Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. Synaptosome
D013779 Tetrodotoxin An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order TETRAODONTIFORMES, which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. Fugu Toxin,Tarichatoxin,Tetradotoxin,Toxin, Fugu

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