Kv2.1 voltage‐gated potassium channel et al . in developmental perspective

Kv2.1 voltage-gated potassium channels consist of two types of alpha-subunits: (a) electrically-active Kcnb1 alpha-subunits and (b) silent or modulatory alpha-subunits plus beta-subunits that, similar to silent alpha-subunits, also regulate electrically-active subunits. Voltage-gated potassium channels were traditionally viewed, mainly by electrophysiologists, as regulators of the electrical activity of the plasma membrane in excitable cells, a role that is performed by transmembrane protein domains of alpha-subunits that form the electric pore. Genetic studies revealed a role for this region of alpha-subunits of voltage-gated potassium channels in human neurodevelopmental disorders, such as epileptic encephalopathy. The N- and C-terminal domains of alpha-subunits interact to form the cytoplasmic subunit of heterotetrameric potassium channels that regulate electric pores. Subsequent animal studies revealed the developmental functions of Kcnb1-containing voltage-gated potassium channels and illustrated their role during brain development and reproduction. These functions of potassium channels are discussed in this review in the context of regulatory interactions between electrically-active and regulatory subunits.