Sites and Regulation of L-Type Ca²⁺ Channel Ca_v1.2 Phosphorylation in Brain

Ca_v1.2 channel phosphorylation plays an important role in regulating neuronal plasticity by action potential-dependent Ca²⁺ entry. Most studies of Ca_v1.2 regulation by phosphorylation have been reported in heart and muscles. Here, we identified phosphorylation sites of neuronal Ca_v1.2 channel protein purified from rat brain using mass spectrometry. The functional characterization of these phosphorylation sites showed altered voltage-dependent biophysical properties of the channel, without affecting current density. These results show that neuronal Ca_v1.2 channel is regulated by phosphorylation in a complex mechanism involving multiple phosphorylation sites.