| Levetiracetam inhibits Na+-dependent Cl-/HCO3- exchange of adult hippocampal CA3 neurons from guinea-pigs. | |
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MedLine Citation:
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PMID: 15249428 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The novel anticonvulsant levetiracetam (LEV) was tested for effects on bioelectric activity and intracellular pH (pHi) regulation of hippocampal CA3 neurons from adult guinea-pigs. In 4-aminopyridine-treated slices, LEV (10-100 microm) reduced the frequency of action potentials and epileptiform bursts of CA3 neurons by 30-55%, while the shape of these potentials remained largely unchanged. Suppressive effects were reversed by an increase of pHi with trimethylamine (TMA). Using BCECF-AM-loaded slices, we found that LEV (10-50 microm) reversibly lowered neuronal steady-state pHi by 0.19 +/- 0.07 pH units in the presence of extracellular CO2/HCO3- buffer. In the nominal absence of extracellular CO2/HCO3- or in Na+-free CO2/HCO3(-)-buffered solution, LEV had no effect on steady-state pHi. Recovery of pHi subsequent to ammonium prepulses remained unchanged in the absence of CO2/HCO3- buffer, but was significantly reduced by LEV in the presence of CO2/HCO3- buffer. These findings show that LEV inhibits HCO3(-)-dependent acid extrusion, but has no effect on Na+/H+ exchange. LEV did not affect Na+-independent Cl-/HCO3- exchange because intracellular alkalosis upon withdrawal of extracellular Cl- remained unchanged. These data show that LEV at clinically relevant concentrations inhibits Na+-dependent Cl-/HCO3- exchange, lowers neuronal pHi, and thereby may contribute to its anticonvulsive activity. |
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Authors:
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Tobias Leniger; Jan Thöne; Udo Bonnet; Andreas Hufnagel; Dieter Bingmann; Martin Wiemann |
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Publication Detail:
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Type: In Vitro; Journal Article Date: 2004-07-12 |
Journal Detail:
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Title: British journal of pharmacology Volume: 142 ISSN: 0007-1188 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-30 Completed Date: 2005-08-04 Revised Date: 2013-06-09 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 1073-80 Citation Subset: IM |
Copyright Information:
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Copyright 2004 Nature Publishing Group |
Affiliation:
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Department of Neurology, University of Essen, Hufelandstr. 55, Essen 45122, Germany. tobias.leniger@uni-essen.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Action Potentials Animals Anticonvulsants / pharmacology* Buffers Cations, Monovalent Chloride-Bicarbonate Antiporters / antagonists & inhibitors* Guinea Pigs Hippocampus / cytology, drug effects*, physiology Hydrogen-Ion Concentration Neurons / drug effects*, physiology Piracetam / analogs & derivatives*, pharmacology* Sodium / metabolism* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Anticonvulsants; 0/Buffers; 0/Cations, Monovalent; 0/Chloride-Bicarbonate Antiporters; 230447L0GL/etiracetam; 7440-23-5/Sodium; 7491-74-9/Piracetam |
| Comments/Corrections | |
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