Levetiracetam inhibits Na+-dependent Cl-/HCO3- exchange of adult hippocampal CA3 neurons from guinea-pigs

British Journal of Pharmacology
T LenigerM Wiemann

Abstract

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...Continue Reading

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Citations

Dec 16, 2005·Molecular and Cellular Biology·Moritz HentschkeChristian A Hübner
Jul 1, 2008·Therapeutic Advances in Neurological Disorders·Rainer SurgesMatthew C Walker
Jul 3, 2015·Frontiers in Cellular Neuroscience·Anne SinningChristian A Hübner
Apr 27, 2017·Journal of Veterinary Emergency and Critical Care·Susan Blades Golubovic, John H Rossmeisl
Dec 18, 2009·British Journal of Pharmacology·Udo BonnetMartin Wiemann
Apr 17, 2013·Physiological Reviews·Mark D Parker, Walter F Boron
Jun 27, 2018·Pharmacological Reviews·Raul R GainetdinovMark D Berry

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