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

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.