Structure and function of Kv4-family transient potassium channels

Shal-type (Kv4.x) K⁺ channels are expressed in a variety of tissue, with particularly high levels in the brain and heart. These channels are the primary subunits that contribute to transient, voltage-dependent K ⁺ currents in the nervous system (A currents) and the heart (transient outward current). Recent studies have revealed an enormous degree of complexity in the regulation of these channels. In this review, we describe the surprisingly large number of ancillary subunits and scaffolding proteins that can interact with the primary subunits, resulting in alterations in channel trafficking and kinetic properties. Furthermore, we discuss posttranslational modification of Kv4.x channel function with an emphasis on the role of kinase modulation of these channels in regulating membrane properties. This concept is especially intriguing as Kv4.2 channels may integrate a variety of intracellular signaling cascades into a coordinated output that dynamically modulates membrane excitability. Finally, the pathophysiology that may arise from dysregulation of these channels is also reviewed.