Depolarization preconditioning produces cytoprotection against veratridine-induced chromaffin cell death.
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.
Orozco
Camilo
C
Instituto de Farmacología Teófilo Hernando, Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo, 4, 28029 Madrid, Spain.
García-de-Diego
Antonio M
AM
Arias
Esperanza
E
Hernández-Guijo
Jesús M
JM
García
Antonio G
AG
Villarroya
Mercedes
M
López
Manuela G
MG
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*
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