Modulation of Ca(2+)-stimulated glutamate release from synaptosomes by Na+ entry through tetrodotoxin-sensitive channels.
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.
Romano-Silva
M A
MA
Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Gomez
M V
MV
Brammer
M J
MJ
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006096:Gramicidin / Q000494:pharmacology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology*
D012604:Scorpion Venoms; D015222:Sodium Channels; D006096:Gramicidin; C003609:tityustoxin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D011189:Potassium Chloride; D012964:Sodium; D002118:Calcium