Akt Activation Is Necessary for Growth Factor–Induced Trafficking of Functional KCaChannels in Developing Parasympathetic Neurons

Abstract

The protein kinase Akt is a crucial regulator of neuronal survival and apoptosis. Here we show that Akt activation is necessary for mobilization of large-conductance KCachannels in ciliary ganglion (CG) neurons evoked by β-neuregulin-1 (NRG1) and transforming growth factor-β1 (TGFβ1). Application of NRG1 to embryonic day 9 (E9) CG neurons increased Akt phosphorylation, as observed previously for TGFβ1. NRG1- and TGFβ1-evoked stimulation of KCais blocked by inhibitors of PI3K by overexpression of a dominant-negative form of Akt, by overexpression of CTMP, an endogenous negative regulator of Akt, and by application of the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-( R)-2- O-methyl-3- O-octadecylcarbonate (HIMO). Conversely, overexpression of a constitutively-active form of Akt was sufficient by itself to increase mobilization of functional KCachannels. NRG1 and TGFβ1 evoked an Akt-dependent increase in cell-surface SLO α-subunits. These procedures have no effect on voltage-activated Ca2+currents. Thus Akt plays an essential role in the developmental regulation of excitability in CG neurons.