• KV2.1

    High-throughput functional screening of KV2.1 variants using the SyncroPatch 768PE system

    Kang et al., 2019

KV2.1 | Shab Related Potassium Channel Member 1

Family:
Potassium channels

Subgroups:
Shaker (KV1.1–KV1.8), Shab (KV2.1-KV2.2), Shaw (KV3.1–KV3.4), Shal (KV4.1–KV4.3), KQT like (KV7.1–KV7.5), Eag related (KV10.1-KV10.2), Erg related (KV11.1–KV11.3), Elk related (KV12.1)

Topology:
Contains six transmembrane domains (S1–S6), four single subunits form a pore, homotetramers and heterotetramers are possible.

KV2.1 Background Information

KV2.1 belongs to the delayed rectifier class and is found throughout the body. It mainly contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain. KCNB1 (gene) can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2 or other alpha subunits, creating a functionally diverse range of channel complexes. Homotetrameric channels display delayed-rectifier voltage- dependent potassium currents which are activated during membrane depolarization (msec range), and inactivated very slowly (range of 5 sec).

Gene:
KCNB1

Human Protein:
UniProt Q14721

Tissue:
Central nervous system, pulmonary arteries, heart, pancreas

Function/ Application:
In mammalian CNS neurons, KCNB1 is a predominant delayed rectifier potassium current that regulates neuronal excitability, action potential duration, and tonic spiking. KCNB1 also contributes to the function and regulation of smooth muscle fibers. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus. Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion. Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions.

Pathology:
Alzheimers Disease, Epileptic Encephalopathy, Early Infantile (26), Undetermined Early-Onset Epileptic Encephalopathy

Interaction:
Forms homotertamers or heterotetramers with KCNB2 or other alpha subunits as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1. Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3. Interacts with STX1A, SNAP25, VAMP2, CREB1, MYL12B, PIAS3, SUMO1, PTPRE. syntaxin, 

Modulator:
hanatoxin, stromatoxin, heteroscordratoxin, guangxitoxin, tetraethylammonium (TEA), 4-aminopyridine (4-AP)

Assays:
Patch Clamp: whole cell mode

Recommended Reviews:
Gutman et al. (2005) International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels. Pharmacol Rev 57(4):473-508

Publications

2019 - Spectrum of KV2.1 Dysfunction in KCNB1‐Associated Neurodevelopmental Disorders

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) Publication Annals of Neurology (2019)

Authors: 
Kang, S.K., Vanoye, C.G., Misra, S.N., Echevarria, D.M., Calhoun, J.D., O’Connor, J.B., Fabre, K.L., McKnight, D., Demmer, L., Goldenberg, P., Grote, L.E., Thiffault, I., Saunders, C., Strauss, K.A., Torkamani, A., van der Smagt, J., van Gassen, K., Carson, R.P., Diaz, J., Leon, E., Jacher, J.E., Hannibal, M.C., Litwin, J., Friedman, N.R., Schreiber, A., Lynch, B., Poduri, A., Marsh, E.D., Goldberg, E.M., Millichap, J.J., George Jr., A.L., Kearney, J.A.

2019 - High Throughput Characterization of KCNB1 Variants Associated with Developmental and Epileptic Encephalopathy

icon sp96  SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) Pre-publication in bioRxiv (2019)

Authors: 
Kang, S.K., Vanoye, C.G., Misra, S.N., Echevarria, D.M., Calhoun, J.D., O’Connor, J.B., Fabre, K.L., McKnight, D., Demmer, L., Goldenberg, P., Grote, L.E., Thiffault, I., Saunders, C., Strauss, K.A., Torkamani, A., van der Smagt, J., van Gassen, K., Carson, R.P., Diaz, J., Leon, E., Jacher, J.E., Hannibal, M.C., Litwin, J., Friedman, N.R., Schreiber, A., Lynch, B., Poduri, A., Marsh, E.D., Goldberg, E.M., Millichap, J.J., George Jr., A.L., Kearney, J.A.

2019 - A Kinetic Map of the Homomeric Voltage-Gated Potassium Channel (Kv) Family

 icon pl   Patchliner publication in Frontiers in Cellular Neuroscience (2019)

Authors:
Ranjan R., Logette E., Marani M., Herzog M., Tâche V., Scantamburlo E., Buchillier V., Markram H.

2017 - Characterization of a KCNB1 variant associated with autism, intellectual disability, and epilepsy

icon sp96  SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in Neurology Genetics (2017)

Authors: 
Calhoun, J.D., Vanoye, C.G., Kok, F., George, A.L., Kearney, J.A.

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