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Evidence for the Induction of Repetitive Action Potentials in Synaptosomes by K + ‐Channel Inhibitors: An Analysis of Plasma Membrane Ion Fluxes
Author(s) -
Tibbs Gareth R.,
Dolly J. Oliver,
Nicholls David G.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.67010389.x
Subject(s) - veratridine , 4 aminopyridine , chemistry , depolarization , biophysics , synaptosome , tetrodotoxin , ouabain , membrane , efflux , membrane potential , potassium channel , chromatography , biochemistry , sodium , sodium channel , biology , organic chemistry
The effects of four K + ‐channel inhibitors on synaptosomal free Ca 2+ concentrations and 86 Rb + fluxes are analysed. 4‐Aminopyridine, α‐dendrotoxin, charybdotoxin, and tetraethylammonium all increase the free Ca 2+ concentration, although their potencies differ widely. In each case, the elevation in free Ca 2+ concentration is reversed by the subsequent addition of tetrodotoxin. The transient 86 Rb + efflux from preequilibrated synaptosomes induced with high concentrations of veratridine is partially inhibited by 4‐aminopyridine and α‐dendrotoxin. In contrast, when 4‐aminopyridine or α‐dendrotoxin is added to polarized synaptosomes, an enhanced 86 Rb + flux is seen, both for uptake and for efflux with no change in the total 86 Rb + /K + content of the synaptosomes and with only a slight time‐averaged plasma membrane depolarization (6.4 and 3.3 mV, respectively). The enhancements of flux by 4‐aminopyridine or α‐dendrotoxin are sensitive to ouabain and/or to tetrodotoxin. Furthermore, these flux changes show the same concentration dependencies as the blocked component of veratridine‐stimulated 86 Rb + efflux, the elevation of free Ca 2+ concentration, and the facilitation of glutamate exocytosis that are elicited by 4‐aminopyridine or α‐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 86 Rb + flux is a consequence of the activity of 4‐aminopyridine‐ and α‐dendrotoxin‐insensitive K + channels during these action potentials.