High spatial density is associated with non-conducting Kv channels from two families.

Ion channels are well known for their ability to regulate the cell membrane potential. However, many ion channels also have functions that do not involve ion conductance. Kv2 channels are one family of ion channels whose non-conducting functions are central to mammalian cell physiology.

Kv2 channel-AMIGO β-subunit assembly modulates both channel function and cell adhesion molecule surface trafficking.

The Kv2 channels encode delayed rectifier currents that regulate membrane potential in many tissues. They also have a non-conducting function to form stable junctions between the endoplasmic reticulum and plasma membranes, creating membrane contact sites that mediate functions distinct from membrane excitability. Therefore, proteins that interact with Kv2.

Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB.

Kv2.1 exhibits two distinct forms of localization patterns on the neuronal plasma membrane: One population is freely diffusive and regulates electrical activity via voltage-dependent K conductance while a second one localizes to micrometer-sized clusters that contain densely packed, but nonconducting, channels. We have previously established that these clusters represent endoplasmic reticulum/plasma membrane (ER/PM) junctions that function as membrane trafficking hubs and that Kv2.

Synthesis of (±)-Tetrabenazine by Visible Light Photoredox Catalysis.

(±)-Tetrabenazine was synthesized in six steps from commercially available compounds. The key cyclization substrate was assembled rapidly via Baylis-Hillman and aza-Michael reactions. Annulation of the final ring was achieved through visible light photocatalysis, wherein carbon-carbon bond formation was driven by the oxidation of a tertiary amine.