KCND2

Description

The KCND2 (potassium voltage-gated channel subfamily D member 2) is a protein-coding gene located on chromosome 7.

Potassium voltage-gated channel subfamily D member 2 is a protein that in humans is encoded by the KCND2 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

== Description == Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member mediates a rapidly inactivating, A-type outward potassium current which is not under the control of the N terminus as it is in Shaker channels.

== Interactions == KCND2 has been shown to interact with FLNC.

== See also == Voltage-gated potassium channel

== References ==

== Further reading ==

== External links == Kv4.2+Potassium+Channel at the U.S. National Library of Medicine Medical Subject Headings (MeSH) KCND2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

KCND2 is a voltage-gated potassium channel that primarily functions in the brain, mediating the dendritic A-type current (I(SA)). This current, active below action potential thresholds, regulates neuronal excitability, influencing factors like latency to spiking, firing frequency, action potential duration, and back-propagation. It also contributes to circadian rhythm regulation in the suprachiasmatic nucleus, impacting locomotor activity. KCND2 is downstream of the metabotropic glutamate receptor GRM5, influencing neuronal excitability and nociception. While it mediates the transient outward current (I(to)) in rodent heart cells, it does not in human hearts, where a different family member performs this function. KCND2 forms tetrameric potassium-selective channels, allowing potassium ions to move along their electrochemical gradients. The channel can switch between open and closed states based on the voltage difference across the membrane. It can form homotetramers or heterotetramers with KCND3, with channel properties influenced by the specific alpha subunits. KCND2 interacts with regulatory subunits like KCNIP1, KCNIP2, KCNIP3, and KCNIP4, enhancing cell surface expression, channel activity, and modulating kinetics. Interaction with DPP6 and DPP10 also promotes membrane expression and regulates channel activity. Upon depolarization, the channel transitions through resting closed (C), activated but non-conducting (C*), inactivated (I), and open (O) states. KCND2 can form homotetramers or heterotetramers with KCND1 or KCND3 and associates with regulatory subunits KCNIP2, KCNIP3, and KCNIP4. Its interaction with KCNIP1 influences N- and C-terminus capture, affecting inactivation and stabilizing the S6 conformation, thereby accelerating closed-state inactivation and recovery. In vivo, KCND2 likely exists as a heteromeric complex containing varying proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6, and DPP10. The tetrameric channel can associate with up to four regulatory subunits, like KCNIP2 or KCNIP4. Interactions with four KCNIP4 chains do not inhibit DPP10 interaction. KCND2 interacts with DLG4 and NCS1/FREQ, as well as DLG1. It is likely part of a complex comprising KCNIP1, KCNIP2 isoform 3, and KCND2. KCND2 interacts with FLNA, FLNC, and DPP10. Its interaction with DPP6 through S1 and S2 helices stabilizes the conformation of these helices and facilitates S4 conformational changes, accelerating activation, inactivation, and recovery.

KCND2 is also known as KV4.2, RK5.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing