Depletion of the Ca(++)-dependent releasable pool of glutamate in striatal synaptosomes associated with dendrotoxin-induced potassium channel blockade

J Neural Transm Gen Sect. 1990;80(3):167-79. doi: 10.1007/BF01245118.

Abstract

The presynaptic actions of the potassium channel blocker Dendrotoxin (DTX) on the Ca+2-dependent release of endogenous glutamate (GLU) and aspartate (ASP) have been tested in synaptosome-enriched preparations from rat striatum. 24 hours after the intrastriatal administration of DTX the K(+)-evoked release of GLU and ASP from the striatal synaptosomes was decreased by 40-45%. No changes in the total synaptosomal content of the amino acids were observed. Superfusion of immobilized synaptosomes with DTX or 4-amino-pyridine resulted in a dose-dependent increase in the basal outflow of GLU and ASP. The release of GLU stimulated by DTX was Ca+2-dependent and was not abolished by superfusing the synaptosomes with 50 microM D-ASP. Moreover, continuous superfusion of DTX (7 microM) to synaptosomes almost completely dumped the subsequent release of GLU and ASP stimulated by 20 mM K+. It is concluded that blockade of presynaptic K+ channels by DTX leads to a massive release of the transmitter pool of GLU (and possible also ASP) from isolated nerve terminals and to a depletion of the amino acid releasable pool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aspartic Acid / metabolism
  • Calcium / metabolism
  • Calcium / physiology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiology*
  • Elapid Venoms / pharmacology*
  • Glutamates / metabolism*
  • Glutamic Acid
  • Male
  • Potassium Channels / drug effects
  • Potassium Channels / physiology*
  • Rats
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Synaptosomes / physiology

Substances

  • Elapid Venoms
  • Glutamates
  • Potassium Channels
  • Aspartic Acid
  • Glutamic Acid
  • dendrotoxin
  • Calcium