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 microM), 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 approximately 120%, also in the presence of tetrodotoxin (TTX) (by approximately 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.
Jauch
Regina
R
Johannes-Müller-Institut für Physiologie, Humboldt Universität, Berlin, Germany.
Windmüller
Olaf
O
Lehmann
Thomas-Nicolas
TN
Heinemann
Uwe
U
Gabriel
Siegrun
S
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002021:Buffers; D004232:Diuretics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005665:Furosemide / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007478:Iontophoresis; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012598:Sclerosis; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D002021:Buffers; D004232:Diuretics; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D000644:Quaternary Ammonium Compounds; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C052377:tetrapropylammonium; D001464:Barium; D013779:Tetrodotoxin; D010042:Ouabain; D015763:2-Amino-5-phosphonovalerate; D005665:Furosemide; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium