Effects of barium, furosemide, ouabaine and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) on ionophoretically-induced changes in extracellular potassium concentration in hippocampal slices from rats and from patients with epilepsy

Glial cells limit local K +-accumulation by K +-uptake through different mechanisms, sensitive to Ba 2+, ouabaine, furosemide, or DIDS. Since the relative contribution of these mechanisms has not yet been determined, we studied the effects of bath-applied barium (2 mM), ouabaine (9 μM), furosemide (2 mM), and DIDS (1 mM) on ionophoretically-induced rises in [K +] o in the pyramidal layer of area CA1 from normal rat slices, in the presence of glutamate receptor (Glu-R) antagonists. We also investigated the effect of barium on ionophoretically-induced tetrapropylammonium (TPA +)-signals in order to test for barium-induced changes of the extracellular space. Finally, we repeated the barium experiment on slices from human non-sclerotic and sclerotic hippocampal specimens to assess a reduced glial capability for barium-sensitive K +-uptake in sclerotic tissue from epilepsy patients. In normal rat slices barium augmented ionophoretically-induced rises in [K +] o by ∼120%, also in the presence of tetrodotoxin (TTX) (by ∼150%), but did not significantly affect the TPA +-signal. Ouabaine also augmented the K +-signal, but only by 27%. Furosemide and DIDS had negligible effects. In slices from sclerotic human hippocampus an augmentation of the K +-signal by barium was absent. Thus barium augments ionophoretically-induced K +-signals to a similar extent as previously shown for stimulus-induced signals. We suggest that glial barium-sensitive K +-buffer mechanisms reduce fast local rises of [K +] o by at least 50%. This capability of glial cells is extremely reduced in area CA1 of slices from human sclerotic hippocampal specimens.