Effects of potassium channel blockade on endogenous glutamate release from cerebellar slices

The effects of potassium channel blockade on the spontaneous release of endogenous glutamate from rat cerebellar slices was studied. Tetrapentylammonium (TPeA), 4-aminopyridine and quinine all increased the spontaneous release of glutamate. The effect of TPeA and 4-AP was potentiated in the absence of Ca2+ from the perfusing fluid. In normal artificial cerebrospinal fluid (ACSF) the Ca2+ channel antagonist, verapamil, mimicked the effects of TPeA seen in Ca2+-free ACSF. The increased release of glutamate produced by TPeA under Ca2+-free conditions was inhibited by the sodium channel blocker, tetrodotoxin, and by Ruthenium red, which inhibits mobilization of mitochondrial Ca2+. The results suggest that external Ca2+ is not required in the TPeA-induced release of glutamate. It is proposed that the prolongation of depolarization seen with potassium channel blocking drugs enables sufficient sodium to enter the neurone and release Ca2+ from intraneuronal stores in order to facilitate transmitter release.