Akt-Dependent Potentiation of L Channels by Insulin-Like Growth Factor-1 Is Required for Neuronal Survival

摘要: The insulin-like growth factor-1 (IGF-1)/receptor tyrosine kinase recently has been shown to mediate neuronal survival and potentiate the activity of specific calcium channel subtypes; requires Akt, a serine/threonine kinase. We demonstrate here that Akt mediates IGF-1-induced potentiation L currents, but not N channels. Transient expression wild-type, dominant–negative, constitutively active forms in cerebellar granule neurons causes, respectively, no change IGF-1/L potentiation, complete inhibition dramatic increase basal currents accompanied by loss ability induce further increases. In case is IGF-1 affected. additionally find partially neuron via Akt-dependent modulation necessary component. Interestingly, very brief exposure (1 min) triggers nearly activity. These results strongly suggest receptor kinases can control long-term calcium-dependent processes rapid voltage-sensitive