title: Depolarization preconditioning produces cytoprotection against veratridine-induced chromaffin cell death.
abstract: The hypothesis that K(+) channels and cell depolarization are involved in neuronal death and neuroprotection was tested in bovine chromaffin cells subjected to two treatment periods: the first period (preconditioning period) lasted 6 to 48 h and consisted of treatment with high K(+) solutions or with tetraethylammonium (TEA), a K(+) channel blocker; the second period consisted of incubation with veratridine for 24 h, to cause cell damage. Preconditioning with high K(+) (20-80 mM) or TEA (10-30 mM) for 24 h caused 20-60% cytoprotection against veratridine-induced cell death in bovine chromaffin cells. The absence of Ca(2+) ions during the first 9 h of an 18-h preconditioning period abolished the cytoprotection. Preconditioning with K(+) or TEA increased by 2.5-fold the expression of brain-derived neurotrophic factor and by nearly 2-fold the expression of the antiapoptotic protein Bcl-2. However, preconditioning did not modify the veratridine-evoked Ca(2+) signal. High K(+) shifted the Em by about 10 mV and TEA evoked a transient burst of action potentials superimposed on a sustained depolarization. We conclude that preconditioning may protect chromaffin cells from death by blocking K(+) channels that depolarize the cell and cause a cytosolic Ca(2+) signal, leading to enhanced expression of BDNF and Bcl-2.
authors.affiliation: Instituto de Farmacología Teófilo Hernando, Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo, 4, 28029 Madrid, Spain.
authors.forename: Camilo
authors.initials: C
authors.lastname: Orozco
authors.forename: Antonio M
authors.initials: AM
authors.lastname: García-de-Diego
authors.forename: Esperanza
authors.initials: E
authors.lastname: Arias
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Hernández-Guijo
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
authors.forename: Mercedes
authors.initials: M
authors.lastname: Villarroya
authors.forename: Manuela G
authors.initials: MG
authors.lastname: López
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology*; D014701:Veratridine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D026902:Potassium Channel Blockers; D019253:Proto-Oncogene Proteins c-bcl-2; D019789:Tetraethylammonium; D011189:Potassium Chloride; D014701:Veratridine; D003513:Cycloheximide; D007770:L-Lactate Dehydrogenase; D002118:Calcium