Common themes in evoked ion channel translocation in neuroplastic and homeostatic plasticity

Ion channel trafficking to and from the plasma membrane is an essential adaptation of neurons to external stimulation, and these distinct processes are tightly regulated by various intrinsic and extrinsic factors. The translocation of ion channels to the plasma membrane can strengthen synaptic connections to enhance and sustain learning and memory. Ion channel translocation can also enhance homeostatic regulation through the creation and maintenance of negative feedback loops. The removal of ion channels from the plasma membrane is critical for preventing hyperexcitability and for achieving homeostatic balance (either of activity or inactivity). Recently described and characterized mechanisms of ion channel exocytosis and endocytosis suggest that a select number of proteins, including specific SNARE isoforms and endophilin, are essential for regulating multiple types of evoked ion channel translocation. Moreover, dysfunction of these key proteins is implicated in the pathophysiology of neurodegenerative diseases and may underly common mechanisms of disease development and progression. This review highlights recent discoveries related to the regulation of evoked ion channel translocation and provides novel insights on how the shared components may contribute to normal functioning and disease states.