EVIDENCE FOR THE INDUCTION OF REPETITIVE ACTION-POTENTIALS IN SYNAPTOSOMES BY K-CHANNEL INHIBITORS - AN ANALYSIS OF PLASMA-MEMBRANE ION FLUXES()

The effects of four K+-channel inhibitors on synaptosomal free Ca2+ co ncentrations and Rb-86(+) fluxes are analysed, 4-Aminopyridine, alpha- dendrotoxin, charybdotoxin, and tetraethylammonium all increase the fr ee Ca2+ concentration, although their potencies differ widely. In each case, the elevation in free Ca2+ concentration is reversed by the sub sequent addition of tetrodotoxin. The transient Rb-86(+) efflux from p reequilibrated synaptosomes induced with high concentrations of veratr idine is partially inhibited by 4-aminopyridine and alpha-dendrotoxin. In contrast, when 4-aminopyridine or alpha-dendrotoxin is added to po larized synaptosomes, an enhanced Rb-86(+) flux is seen, both for upta ke and for efflux with no change in the total Rb-86(+)/K+ content of t he synaptosomes and with only a slight time-averaged plasma membrane d epolarization (6.4 and 3.3 mV, respectively). The enhancements of flux by 4-aminopyridine or alpha-dendrotoxin are sensitive to ouabain and/ or to tetrodotoxin. Furthermore, these flux changes show the same conc entration dependencies as the blocked component of veratridine-stimula ted Rb-86(+) efflux, the elevation of free Ca2+ concentration, and the facilitation of glutamate exocytosis that are elicited by 4-aminopyri dine or alpha-dendrotoxin, It is concluded that these findings support the proposal of spontaneous, repetitive firing of synaptosomes evoked by K+-channel inhibitors and that the enhanced Rb-86(+) flux is a con sequence of the activity of 4-aminopyridine- and alpha-dendrotoxin-ins ensitive K+ channels during these action potentials.