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.