TY - JOUR T1 - Calmodulin Is Involved in Membrane Depolarization-Mediated Survival of Motoneurons by Phosphatidylinositol-3 Kinase- and MAPK-Independent Pathways JF - The Journal of Neuroscience JO - J. Neurosci. SP - 1230 LP - 1239 DO - 10.1523/JNEUROSCI.18-04-01230.1998 VL - 18 IS - 4 AU - Rosa M. Soler AU - Joaquim Egea AU - Gerard M. Mintenig AU - Cesar Sanz-Rodriguez AU - Montse Iglesias AU - Joan X. Comella Y1 - 1998/02/15 UR - http://www.jneurosci.org/content/18/4/1230.abstract N2 - In the present work, we find that the elevation of extracellular K+ concentration promotes the survival of chick spinal cord motoneurons in vitro deprived of any neurotrophic support. This treatment induces chronic depolarization of the neuronal plasma membrane, which activates L-type voltage-dependent Ca2+ channels, resulting in Ca2+influx and elevation of the cytosolic free Ca2+concentration. Pharmacological reduction of intracellular free Ca2+ or withdrawal of extracellular Ca2+ reversed the effects of depolarization on survival. The intracellular Ca2+ response to membrane depolarization developed as an initial peak followed by a sustained increase in intracellular Ca2+concentration. The depolarizing treatment caused tyrosine phosphorylation of mitogen-activated protein kinase (MAPK) without involving tyrosine kinase receptor activation. The calmodulin antagonist W13 inhibited the survival-promoting effect induced by membrane depolarization but not the tyrosine phosphorylation of MAPK. Moreover, depolarization did not induce phosphatidylinositol-3 kinase (PI-3K) phosphorylation in our cells, and the PI-3K inhibitor wortmannin did not suppress the survival-promoting effect of K+ treatment. These results suggest that calmodulin is involved in calcium-mediated survival of motoneurons through the activation of PI-3K- and MAPK-independent pathways. ER -