Ex vivo release of GABA from tetanus toxin-induced chronic epileptic foci decreased during the active seizure phase.
Injecting a few mouse LD(50) of tetanus toxin into rat hippocampus has been shown to induce a remarkably persistent sequence of functional changes which provide a chronic model of limbic epilepsy. Here we have measured the release of amino acid transmitters evoked by K(+)-stimulation from hippocampal slices prepared from rats which had been injected 10-14 days previously with 6 mouse LD(50) (c. 3 ng) of tetanus toxin. The Ca(2+)-dependent component of the release of [(14)C]?-aminobutyric acid (GABA) was depressed to two thirds its control level. Rats which had survived 6-8 weeks, by which time the seizures had ceased, showed a recovery of the Ca(2+)-dependent component of the K(+)-evoked release of GABA to control levels, but these rats also exhibited a paradoxical depression of the Ca(2+)-independent component of release. [(3)H]d-Aspartate has previously been used as a putative marker for excitatory amino acid release. However, it failed to fulfil this role in the present study because its release was not stimulated by K(+). In contrast [(3)H]d-aspartate was released in response to veratrine. Together with previous work this suggests that while [(3)H]d-aspartate was taken up into neurones, it did not enter the releasable vesicular pool. HPLC measurements of the release of endogenous excitatory amino acids showed that glutamate (and not aspartate) was stimulated by K(+) in a Ca(2+)-dependent manner, and that the amount of release did not differ in the tetanus toxin-injected rats. The depression of GABA release provides the most likely mechanism for the seizures. The recovery of its Ca(2+)-dependent release provides the most likely basis for seizure remission after 6-8 weeks, in this chronic epileptic syndrome.
Jefferys
J G
JG
Department of Physiology and Biophysics, Imperial College of Science, Technology and Medicine, London W2 1PG, U.K.
Mitchell
P
P
O'Hara
L
L
Tiley
C
C
Hardy
J
J
Jordan
S J
SJ
Lynch
M
M
Wadsworth
J
J