A-type voltage-gated potassium channel KCND2
Also known as: Kcnd2
Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons. This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation. Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity. Upon depolarization, the channel goes from a resting closed state (C state) to an activated but non-conducting state (C* state), from there, the channel may either inactivate (I state) or open (O state) (By similarity).
Classification
- Family (Pfam)
- PF02214 BTB_2, PF11879 DUF3399, PF00520 Ion_trans, PF11601 Shal-type
- InterPro
- BTB/POZ_dom, Ion_trans_dom, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv4, K_chnl_volt-dep_Kv4.2, K_chnl_volt-dep_Kv4_C, Shal-type_N, SKP1/BTB/POZ_sf, T1-type_BTB, VG_K_chnl, Volt_channel_dom_sf
- Functional cluster
- Protein Serine/Threonine Kinases
Experimental structures · PDB · 2
A predicted model is available from AlphaFold.
Gene Ontology · 40
- GO:0070161 anchoring junction
- GO:0005901 caveola
- GO:0030425 dendrite
- GO:0043197 dendritic spine
- GO:0098982 GABA-ergic synapse
- GO:0098978 glutamatergic synapse
- GO:0071193 Kv4.2-KChIP2 channel complex
- GO:0016020 membrane
- GO:0043025 neuronal cell body
- GO:0032809 neuronal cell body membrane
- GO:0043204 perikaryon
- GO:0097038 perinuclear endoplasmic reticulum
- GO:0005886 plasma membrane
- GO:0044853 plasma membrane raft
- GO:0045211 postsynaptic membrane
- GO:0099634 postsynaptic specialization membrane
- GO:0034705 potassium channel complex
- GO:0042383 sarcolemma
- GO:0030315 T-tubule
- GO:0008076 voltage-gated potassium channel complex
- GO:0005250 A-type (transient outward) potassium channel activity
- GO:0046872 metal ion binding
- GO:0005216 monoatomic ion channel activity
- GO:0005267 potassium channel activity
- GO:0044877 protein-containing complex binding
- GO:1905030 voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
- GO:0005249 voltage-gated potassium channel activity
- GO:0001508 action potential
- GO:0086001 cardiac muscle cell action potential
- GO:0071456 cellular response to hypoxia
- GO:0071260 cellular response to mechanical stimulus
- GO:0071466 cellular response to xenobiotic stimulus
- GO:0045475 locomotor rhythm
- GO:0086009 membrane repolarization
- GO:0006936 muscle contraction
- GO:0019228 neuronal action potential
- GO:0071805 potassium ion transmembrane transport
- GO:0006813 potassium ion transport
- GO:0051260 protein homooligomerization
- GO:0019233 sensory perception of pain
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- A-type voltage-gated potassium channel KCND2 1.00
- A-type voltage-gated potassium channel KCND2 1.00
- A-type voltage-gated potassium channel KCND2 1.00
- A-type voltage-gated potassium channel KCND2 1.00
- A-type voltage-gated potassium channel KCND3 0.96
- A-type voltage-gated potassium channel KCND3 0.95
- A-type voltage-gated potassium channel KCND3 0.95
- A-type voltage-gated potassium channel KCND3 0.95
- Potassium voltage-gated channel protein Shal 0.90
- A-type voltage-gated potassium channel KCND1 0.85
- A-type voltage-gated potassium channel KCND1 0.84
- A-type voltage-gated potassium channel KCND1 0.83
Co-cited proteins · studied together in the literature
- A-type potassium channel modulatory protein DPP6 4 shared papers
- A-type potassium channel modulatory protein KCNIP2 3 shared papers
- Kv channel-interacting protein 4 5 shared papers
- Inactive dipeptidyl peptidase 10 3 shared papers
- Kv channel-interacting protein 4 3 shared papers
- A-type voltage-gated potassium channel KCND2 9 shared papers
- A-type potassium channel modulatory protein KCNIP1 3 shared papers
- Potassium voltage-gated channel subfamily A member 5 1 shared papers
- Calsenilin 4 shared papers
- Calsenilin 4 shared papers
- A-type voltage-gated potassium channel KCND2 3 shared papers
- Potassium channel toxin TsTXK-beta/Cryptide TyPep-16 1 shared papers
Literature · 53 cited papers
- Ts8 scorpion toxin inhibits the Kv4.2 channel and produces nociception in vivo. Toxicon · 2016
- Regulation of Kv4.2 A-type potassium channels in HEK-293 cells by hypoxia. Front. Cell. Neurosci. · 2014
- The stoichiometry and biophysical properties of the Kv4 potassium channel complex with K+ channel-interacting protein (KChIP) subunits are variable, depending on the relative expression level. J. Biol. Chem. · 2014
- Localization of Kv4.2 and KChIP2 in lipid rafts and modulation of outward K(+) currents by membrane cholesterol content in rat left ventricular myocytes. Pflugers Arch. · 2015
- Local plasticity of dendritic excitability can be autonomous of synaptic plasticity and regulated by activity-based phosphorylation of Kv4.2. PLoS ONE · 2014
- Distribution and functional expression of Kv4 family alpha subunits and associated KChIP beta subunits in the bed nucleus of the stria terminalis. J. Comp. Neurol. · 2014
- Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat. Commun. · 2012
- Unique somato-dendritic distribution pattern of Kv4.2 channels on hippocampal CA1 pyramidal cells. Eur. J. Neurosci. · 2012
- Alpha1-adrenoceptors regulate only the caveolae-located subpopulation of cardiac K(V)4 channels. Channels · 2010
- KChIP4a regulates Kv4.2 channel trafficking through PKA phosphorylation. Mol. Cell. Neurosci. · 2010
- A novel N-terminal motif of dipeptidyl peptidase-like proteins produces rapid inactivation of KV4.2 channels by a pore-blocking mechanism. Channels · 2009
- Convergent modulation of Kv4.2 channel alpha subunits by structurally distinct DPPX and KChIP auxiliary subunits. Biochemistry · 2009
- … and 41 more in the literature graph