Potassium channel subfamily K member 5 (KCNK5) (KCNK5)

The Flicker potassium channel, molecularly identified as the Potassium channel subfamily K member 5 (KCNK5 or TASK-2), is a member of the two-pore domain potassium (K2P) channel family. It is characterized by its voltage-independent "leak" conductance and a tendency to "flicker" between open and closed states in electrophysiological recordings. Primarily expressed in the axonal membranes of myelinated and unmyelinated nerve fibers, as well as in the kidney and other epithelia, it plays a crucial role in maintaining the resting membrane potential and modulating cellular excitability. In the nervous system, the Flicker potassium channel is a significant secondary target for local anesthetics such as lidocaine and bupivacaine; its inhibition leads to partial depolarization, which facilitates the blockade of voltage-gated sodium channels and contributes to the analgesic effect. In the kidney, KCNK5 is involved in bicarbonate reabsorption and volume regulation. Dysregulation or genetic variants of this channel have been linked to conditions such as Balkan endemic nephropathy and altered pain sensitivity.

Other names

Flicker potassium channelTASK-2TWIK-related acid-sensitive K+ channel 2K2P5.1Potassium channel, two-pore domain, subfamily K, member 5

Local anesthetics inhibit the Flicker potassium channel (KCNK5), which is a background leak channel responsible for maintaining the resting membrane potential. Inhibition leads to a slight depolarization of the axonal membrane, which increases the fraction of voltage-gated sodium channels in the inactivated state, thereby lowering the threshold for conduction block and enhancing the anesthetic effect.