Kv2.1 voltage‐gated potassium channels in developmental perspective

Abstract

Kv2.1 voltage‐gated potassium channels consist of two types of α‐subunits: (a) electrically‐active Kcnb1 α‐subunits and (b) silent or modulatory α‐subunits plus β‐subunits that, similar to silent α‐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 α‐subunits that form the electric pore. Genetic studies revealed a role for this region of α‐subunits of voltage‐gated potassium channels in human neurodevelopmental disorders, such as epileptic encephalopathy. The N‐ and C‐terminal domains of α‐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.

Cdyl Deficiency Brakes Neuronal Excitability and Nociception through Promoting Kcnb1 Transcription in Peripheral Sensory Neurons

“…K v 2.1 channel is well known to function as a suppressor of neuronal excitability especially when high‐frequency AP firing happens and exerts neuroprotection under various hyperexcitable conditions. [ 24 , 25 , 26 ] DRG neurons from Cdyl cKO mice and controls were treated with GxTX‐1E, a specific inhibitor of K v 2.1 channel, [ 19 , 27 ] to explore whether K v 2.1 channel contributed to the regulation of CDYL on intrinsic excitability. Repression of functional K v 2.1 channel did not influence the RMP and other AP parameters (Figure S5a–e , Supporting Information).…”

Retinoschisin and novel Na/K-ATPase interaction partners Kv2.1 and Kv8.2 define a growing protein complex at the inner segments of mammalian photoreceptors

“…Disruption of this interaction resulted in increased calcium sparks and waves, a possible mechanism for arrhythmogenesis in the AnkB syndrome [ 63 ]. Also, pathogenic mutations in KCNB1 encoding the Kv2.1 subunit, have been identified in patients with different neurodevelopmental disorders like epilepsy or autism [ 64 ]. Further, Kv2.1 knockout mice manifest neuronal and behavioral hyperexcitability [ 65 ], as well as retinal dysfunction.…”

Retinoschisin and novel Na/K-ATPase interaction partners Kv2.1 and Kv8.2 define a growing protein complex at the inner segments of mammalian photoreceptors

“…Disruption of this interaction resulted in increased calcium sparks and waves, a possible mechanism for arrhythmogenesis in the AnkB syndrome [41]. Also, pathogenic mutations in KCNB1 encoding the Kv2.1 subunit, have been identi ed in patients with different neurodevelopmental disorders like epilepsy or autism [42]. Further, Kv2.1 knockout mice manifest neuronal and behavioral hyperexcitability [43], as well as retinal dysfunction.…”