Rat Cortical Synaptosomes Have More Than One Mechanism for Ca2+ Entry Linked to Rapid Glutamate Release: Studies Using the Phoneutria Nigriventer Toxin PhTX2 and Potassium Depolarization

Overview

Journal Biochem J

Specialty Biochemistry

Date 1993 Dec 1

PMID 7504921

Citations 14

Authors

M A Romano-Silva

A M Ribeiro

M V Gomez

C R DINIZ

M N Cordeiro

M J Brammer

Affiliations

Soon will be listed here.

Abstract

PhTX2, one of the components of the venom of the South American spider Phoneutria nigriventer, inhibits the closure of voltage-sensitive Na+ channels. Incubation of cerebral-cortical synaptosomes with PhTX2 causes a rapid increase in the intrasynaptosomal free Ca2+ concentration and a dose-dependent release of glutamate. This release is made up of a slow component, which appears to be due to reversal of Na(+)-dependent glutamate uptake, and more rapid component that is dependent on the entry of extrasynaptosomal Ca2+. It has previously been shown that membrane depolarization using KCl can cause rapid Ca(2+)-dependent release of glutamate from synaptosomes. This requires Ca2+ entry through a specific type of Ca2+ channel that is sensitive to Aga-GI, a toxic component of the venom of the spider Agelenopsis aperta. We have compared the effects of PhTX2 and KCl on elevation of intrasynaptosomal free Ca2+ and glutamate release, and a number of differences have emerged. Firstly, PhTX2-mediated Ca2+ influx and glutamate release, but not those caused by KCl, are inhibited by tetrodotoxin. Secondly, KCl produces a clear additional increase in Ca2+ and glutamate release following those elicited by PhTX2. Finally, 500 microM MnCl2 abolishes PhTX2-mediated, but not KCl-mediated, glutamate release. These findings suggest that more than one mechanism of Ca2+ entry may be coupled to glutamate release from nerve endings.

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