The life cycle of voltage-gated Ca(2+) channels in neurons: an update on the trafficking of neuronal calcium channels

Neuronal voltage-gated Ca(2+) (Ca(V)) channels play a critical role in cellular excitability, synaptic transmission, excitation–transcription coupling and activation of intracellular signaling pathways. Ca(V) channels are multiprotein complexes and their functional expression in the plasma membrane involves finely tuned mechanisms, including forward trafficking from the endoplasmic reticulum (ER) to the plasma membrane, endocytosis and recycling. Whether genetic or acquired, alterations and defects in the trafficking of neuronal Ca(V) channels can have severe physiological consequences. In this review, we address the current evidence concerning the regulatory mechanisms which underlie precise control of neuronal Ca(V) channel trafficking and we discuss their potential as therapeutic targets.