Akt-dependent potentiation of L channels by insulin-like growth factor-1 is required for neuronal survival

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; survival requires Akt, a serine/threonin e kinase. We demonstrate here that Akt mediates the IGF-1-induced potentiat ion of L channel currents, but not that of N channels. Transient expression of wild-type, dominant-negative, and constitutively active forms of Akt in cerebellar granule neurons causes, respectively, no change in IGF-1/L chan nel potentiation, complete inhibition of potentiation, and a dramatic incre ase in basal L currents accompanied by the loss of ability to induce furthe r increases. In no case is the IGF-1 potentiation of N currents affected. W e additionally find that IGF-1 partially mediates granule neuron survival v ia L channel activity and that Akt-dependent L channel modulation is a nece ssary component. Interestingly, very brief exposure (1 min) to IGF-1 trigge rs nearly complete survival and requires L channel activity. These results strongly suggest that neuronal receptor tyrosine kinases can control long-t erm calcium-dependent processes via the rapid control of voltage-sensitive channels.