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The Survival of Sympathetic Neurons Promoted by Potassium Depolarization, but Not by Cyclic AMP, Requires Phosphatidylinositol 3‐Kinase and Akt
Author(s) -
Crowder Robert J.,
Freeman Robert S.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.730466.x
Subject(s) - protein kinase b , depolarization , ly294002 , protein kinase a , phosphatidylinositol , biology , microbiology and biotechnology , kinase , chemistry , endocrinology , signal transduction
: Phosphatidylinositol (PI) 3‐kinase and Akt protein kinase mediate trophic factor‐dependent survival in certain neurons. However, a role for these enzymes in neuronal survival promoted by other agents is unclear. We have tested PI 3‐kinase and Akt for their role in survival promoted by membrane‐depolarizing concentrations of extracellular potassium and the cell‐permeable cyclic AMP analogue 8‐(4‐chlorophenylthio)cyclic AMP (cpt‐cAMP). Depolarization of sympathetic neurons resulted in an increase in the activities of both PI 3‐kinase and Akt. In addition, the PI 3‐kinase inhibitor LY294002 was a potent inducer of cell death in depolarized neurons. Stimulation with cpt‐cAMP resulted in relatively small increases in PI 3‐kinase and Akt activities, and neurons maintained with cpt‐cAMP were more resistant to LY294002‐induced death than were depolarized neurons. Expression of either dominant‐negative PI 3‐kinase or dominant‐negative Akt blocked survival promoted by depolarization but not by cpt‐cAMP. These results indicate that a PI 3‐kinase/Akt pathway is required for survival of sympathetic neurons mediated by depolarization but not by cpt‐cAMP. Thus, the survival of sympathetic neurons can be maintained through PI 3‐kinase/Akt‐dependent and‐independent pathways.