KV1.1 | Shaker 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.

KV1.1 Background Information

KV1.1 is a delayed-rectifier voltage gated potassium channel that mediates transmembrane potassium transport in excitable membranes. It Contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability. It is suggested that heteromeric potassium channels composed of both KV1.1 and KV1.2 play a role in pacemaking and regulate the output of deep cerebellar nuclear neuron

Gene:
KCNA1

Human Protein:
UniProt Q09470

Tissue:
CNS, kidney

Function/ Application:
KV1.1 contributes to the regulation of the membrane potential and nerve signaling, and prevents neuronal hyperexcitability. The channel regulates neuronal excitability in hippocampus, especially in mossy fibers and medial perforant path axons. The regulation of the hyperexcitability in myelinated axons of the vagus nerve may contribute to the regulation of heart contraction. Furthermore, the channel plays a role in the reabsorption of Mg2+ in the distal convoluted tubules in the kidney and in magnesium ion homeostasis, probably via its effect on the membrane potential

Pathology:
Mutations in this gene cause episodic ataxia type 1 (EA1) and Myokymia isolated 1 (MK1), the Isaacs syndrome is a result of an autoimmune reaction against the Kv1.1 ion channel

Interaction:
KCNA1 can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well. Channel properties are modulated by cytoplasmic beta subunits (KCNAB1 and KCNAB2) that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. Furthermore the channel can interact with: Futher interactions: ANK3, KCNRG, GNB1, GNG2, STX1A, LGI1, DLG1, DLG2 and DLG4

Modulator:
4-aminopyridine (4-AP), tetraethylammonium (TEA), dendrotoxin (DTX), Amitriptyline, Retigabine

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

Useful website:
https://channelpedia.epfl.ch/ionchannels/2

Publications

2020 - Structural basis of the potency and selectivity of Urotoxin, a potent Kv1 blocker from scorpion venom

icon pl   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 - Discovery of a small molecule modulator of the Kv1.1/Kvβ1 channel complex that reduces neuronal excitability and in vitro epileptiform activity

icon pl   Patchliner publication in CNS Neuroscience & Therapeutics (2019)

Authors:
Niespodziany I., Mullier B., André V.M., Ghisdal P., Jnoff E., Moreno‐Delgado D., Swinnen D., Sands Z., Wood M., Wolff C.

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.

2014 - A potent and Kv1.3-selective analogue of the scorpion toxin HsTX1 as a potential therapeutic for autoimmune diseases

icon pap  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

icon pap   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.

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