KV1.3 | Shaker Related Potassium Channel Member 3
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.
KV1.3 Background Information
KV1.3 belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. KV1.3 is expressed in T and B lymphocytes and plays an essential role in T cell proliferation and activation. Blockade of KV1.3 channels in effector-memory T cells suppresses calcium signaling, cytokine production (interferon-gamma, interleukin 2) and cell proliferation. KV1.3 is an important target for drug development for autoimmune diseases as Multiple Sclerosis, type-1 diabetes mellitus and rheumatoid arthritis.
Gene:
KCNA3
Human Protein:
UniProt P22001
Tissue:
brain, lung, osteoclasts, T-lymphocytes, B-lymphocytes
Function/ Application:
T-lymphocyte activation, apoptosis, proliferation
Pathology:
Immune response, multiple sclerosis, rheumatoid arthritis, diabetes mellitus, asthma, cancer
Interaction:
KVβ2, β1 Integrin, SAP97, ZIP
Modulator:
PAP-1, Margatoxin, Noxiustoxin, Charybdotoxin
Assays:
Patch Clamp: whole cell, room temperature, physiological temperature, State- and use-dependence / site of action
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
Data and Applications
KV1.3 - Colour Coding Displays Real Gigaohm Seals
SyncroPatch 96 (a predecessor model of SyncroPatch 384PE) data and applications:
Cells were kindly provided by Evotec AG, Hamburg, Germany.
Shown is a screenshot made during a recording of KV1.3 currents stably expressed in CHO cells. On the top left the raw currents from each individual cell are displayed. The background color coding marks the cells with seals above 500 MΩ in blue and above 1 GΩ in green.
KV1.3 - Continuous Internal Perfusion
Port-a-Patch data and applications:
KV1.3 currents (blue), endogenously expressed in Jurkat cells, were rapidly blocked by internal perfusion of Cs+ (light blue), and fully recovered after washout with K+ (grey). Internal solution replacement was repeated 19 times and the recording was stable for over 35 minutes, as shown in the lower graph.
KV1.3 - Internal Application of TEA and Quinidine
Port-a-Patch data and applications:
KV1.3 current was blocked by the internal application of increasing concentrations of quinidine (left) or TEA+ (right). For quinidine the IC50 was determined as 15 μM (literature value external application 14 μM) and for TEA+ the IC50 was determined as 0.9 ± 0.3 mM (n = 3) (literature value internal application 0.6 mM).
KV1.3 - Internal Solution Exchange during Recording
Patchliner data and applications:
A unique feature of the Patchliner is its ability to exchange the internal solution during the recording. The figure shows recordings of KV1.3 from two Jurkat cells (simultaneoulsy recorded) in the presence of control internal solution, after the exchange of the internal solution with a Cs+ solution, and subsequent washout (left to right).
KV1.3 - Perforated Patch
Port-a-Patch data and applications:
Perforated and conventional whole cell configuration derived hKV1.3-currents. Voltage-dependence was shifted significantly to more negative potentials in the whole cell configuration compared to the perforated whole cell configuration. Whole cell currents after a conventional membrane breakthrough (right) and perforated whole cell currents (left).
KV1.3 - Pharmacology with High Success Rate
SyncroPatch 384PE (a predecessor model of SyncroPatch 384) data and applications:
Cells were kindly provided by Evotec.
Shown are screenshots of a pharmacology experiment performed with the SyncroPatch 384PE (a predecessor model of SyncroPatch 384). Recordings from 384 KV1.3 expressing CHO cells were performed simultaneously. Original current traces and the peak current over time are displayed. Data are analysed with DataControl384 full analysis tool. With just a few mouse-clicks normalized concentration response curves can be generated. Here, normalized response and the IC50 of Quinidine is shown. Darkening shades of blue indicate increasing compound concentration.
KV1.3 - Reproducible Compound Application
Patchliner data and applications:
Application of 5 μM quinidine leads to about 50 % block of the KV1.3 currents (blue). After washout, the current is fully recovered (grey). The lower graph shows corresponding Imax (+40 mV) in the absence and presence of 5 μM quinidine, for two different cells with eight consecutive application and washout steps. The recording lasted over 40 minutes!
KV1.3 - Voltage Induced Membrane Movements Measured with Atomic Force Microscopy
Port-a-Patch data and applications:
Data are taken from Pamir E., et al., Ultramicroscopy, 2008, 108, 552-557.
Voltage induced membrane movements of a Jurkat cell. (a) Deflection signal of the cantilever resting on the cell membrane at an indenting force of 1.0 nN. (b) Corresponding whole cell current: The characteristic response of the voltage gated potassium channel KV1.3 in Jurkat cells is observed. (c) Below: Applied pulse protocol.
Application Notes
KV1.3 - "Automated internal perfusion of Jurkat cells expressing KV1.3 channels"
Port-a-Patch application note: 
(0.2 MB)
KV1.3 - "Pharmacological analysis of heterologous and endogenous expressed KV1.3 channels in Sf21 insect cells and T-lymphocytes"
Patchliner application note: (0.7 MB)
Cells were kindly provided by conoGenetix.
Mitochondria - "Mitoplasts from HEK cells on Nanion‘s Port-a-Patch"
Port-a-Patch application note (0.5 MB)
Publications
2021 - Suppressing Kv1.3 Ion Channel Activity with a Novel Small Molecule Inhibitor Ameliorates Inflammation in a Humanised Mouse Model of Ulcerative Colitis
Patchliner Publication in Journal of Crohn's and Colitis (2021)
Authors:
Unterweger A-L., Jensen M. Ø., Giordanetto F., Jogini V., Rüschher A., Seuß M., Winkelmann P., Koletzko L., Shaw D. E., Siebeck M., Gropp R., Beigel F., Aszodi A.
2020 - Structural basis of the potency and selectivity of Urotoxin, a potent Kv1 blocker from scorpion venom
Patchliner publication in Biochemical Pharmacology (2020)
Authors:
Luna-Ramirez K., Csoti A., McArthur J.R., Chin Y.K.Y., Anangi R., del Carmen Najera R., Possani L.D., King G.F., Panyi G., Yu H., Adams D.J., Finol-Urdaneta R.K.
2019 - KCa1.1 and Kv1.3 channels regulate the interactions between fibroblast-like synoviocytes and T lymphocytes during rheumatoid arthritis
Port-a-Patch publication in Arthritis Research & Therapy (2019)
Authors:
Tanner M.R., Pennington M.W., Chauhan S.S., Laragione T., Gulko P.S., Beeton C.
2019 - A Kinetic Map of the Homomeric Voltage-Gated Potassium Channel (Kv) Family
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.
2018 - Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors
SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) publication in PNAS
Authors:
Chernov-Rogan T., Li T., Lu G., Verschoof H., Khakh K., Jones S.W., Beresini M.H., Liu C., Ortwine D.F., McKerrall S.J., Hackos D.H., Sutherlin D., Cohen C.J., and Chen J.
2017 - Prolonged immunomodulation in inflammatory arthritis using the selective Kv1.3 channel blocker HsTX1[R14A] and its PEGylated analog
Port-a-Patch publication in Clinical Immunology (2017)
Authors:
Tanner M.R., Tajhya R.B., Huq R., Gehrmann E.J., Rodarte K.E., Atik M.A., Norton R.S., Pennington R.W., Beeton C.
2017 - Potassium channels Kv1.3 and KCa3.1 cooperatively and compensatorily regulate antigen-specific memory T cell functions
SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in Nature Communications (2017)
Authors:
Chiang E.Y., Li T., Jeet S., Peng I., Zhang J., Lee W. P., DeVoss J., Caplazi P., Chen J., Warming S., Hackos D.H., Mukund S., Koth C.M., Grogan J.L.
2017 - High-throughput electrophysiological assays for voltage gated ion channels using SyncroPatch 768PE
SyncroPatch 768PE (a predecessor model of SyncroPatch 384/768i) publication in PLoS One (2017)
Authors:
Li T, Lu G, Chiang E.Y., Chernov-Rogan T., Grogan J.L., Chen J.
2016 - Human T cells in silico: Modelling their electrophysiological behaviour in health and disease
Patchliner publication in Journal of Theoretical Biology (2016)
Authors:
Ehling P., Meuth P., Eichinger P., Hermann A.M., Bittner S., Pawlowski M., Pankratz S., Herty M., Budde T., Meuth S.G.
2015 - The two-pore domain K2P channel TASK2 drives human NK-cell proliferation and cytolytic function
Patchliner publication in European Journal of Immunology (2015)
Authors:
Schulte-Mecklenbeck A., Bittner S., Ehling P., Döring F., Wischmeyer E., Breuer J., Herrmann A.M., Wiendl H., Meuth S.G., Gross C.C.
2014 - A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases
Port-a-Patch publication in Nature Scientific Reports (2014)
Authors:
Rashid M.H., Huq R., Tanner M.R., Chhabra S., Khoo K.K., Estrada R., Dhawan V., Chauhan S., Pennington M.W., Beeton C., Kuyucak S., Norton R.S.
2013 - A Potent and Selective Peptide Blocker of the Kv1.3 Channel: Prediction from Free-Energy Simulations and Experimental Confirmation
Port-a-Patch publication in PLoS ONE (2013)
Authors:
Rashid M.H., Heinzelmann G., Huq R., Tajhya R.B., Chang S.C., Chhabra S., Pennington M.W., Beeton C., Norton R.S., Kuyucak S.
2011 - Development of a selective small-molecule inhibitor of Kir1.1, the Renal Outer Medullary Potassium Channel
Patchliner publication in Molecular Pharmacology (2011)
Authors:
Bhave G., Chauder B.A., Liu W., Dawson E.S., Kadakia R., Nguyen T.T., Lewis L.M., Meiler J., Weaver C.D., Satlin L.M., Lindsley C.W., Denton J.S.
2009 - Port-a-Patch and Patchliner: High fidelity electrophysiology for secondary screening and safety pharmacology
Port-a-Patch and Patchliner publication in Combinatorial Chemistry & High Throughput Screening (2009)
Authors:
Farre C., Haythornthwaite A., Haarmann C., Stoelzle S., Kreir M., George M., Brüggemann A., Fertig N.
2008 - Synthesis and biological evaluation of chalcones as inhibitors of the voltage-gated potassium channel Kv1.3
Port-a-Patch publication in Bioorganic & Medicinal Chemistry Letters (2008)
Authors:
Cianci J., Baell J.B., Flynn B.L., Gable R.W., Mould J.A., Paul D., Harvey A.J.
2008 - Planar patch-clamp force microscopy on living cells
Port-a-Patch publication in Ultramicroscopy (2008)
Authors:
Pamir E., George M., Fertig N., Benoit M.
2007 - Automated ion channel screening: patch clamping made easy
Port-a-Patch and Patchliner publication in Expert Opinion Therapeutic Targets (2007)
Authors:
Farre C., Stoelzle S., Haarman C., George M., Brueggemann A., Fertig N.