KCNA5 explained

Potassium voltage-gated channel, shaker-related subfamily, member 5, also known as KCNA5 or K_v1.5, is a protein that in humans is encoded by the KCNA5 gene.^[1]

Function

Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. KCNA5 encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, the function of which could restore the resting membrane potential of beta cells after depolarization, thereby contributing to the regulation of insulin secretion. This gene is intronless, and the gene is clustered with genes KCNA1 and KCNA6 on chromosome 12. Mutations in this gene have been related to both atrial fibrillation^[2] and sudden cardiac death.^[3] KCNA5 are also key players in pulmonary vascular function, where they play a role in setting the resting membrane potential and its involvement during hypoxic pulmonary vasoconstriction.

Interactions

KCNA5 has been shown to interact with DLG4,^{[4] [5]} PDZ domain-containing proteins such as SAP97,^[6] and Actinin, alpha 2.^{[4] [7]}

See also

• Voltage-gated potassium channel

Further reading

• Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stühmer W, Wang X . International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels . Pharmacological Reviews . 57 . 4 . 473–508 . Dec 2005 . 16382104 . 10.1124/pr.57.4.10 . 219195192 .
• Curran ME, Landes GM, Keating MT . Molecular cloning, characterization, and genomic localization of a human potassium channel gene . Genomics . 12 . 4 . 729–37 . Apr 1992 . 1349297 . 10.1016/0888-7543(92)90302-9 .
• Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, Steiner DF . Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel . Proceedings of the National Academy of Sciences of the United States of America . 88 . 1 . 53–7 . Jan 1991 . 1986382 . 50746 . 10.1073/pnas.88.1.53 . 1991PNAS...88...53P . free .
• Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, Glover DM . Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle . FASEB Journal . 5 . 3 . 331–7 . Mar 1991 . 2001794 . 10.1096/fasebj.5.3.2001794. free . 23737559 .
• Mays DJ, Foose JM, Philipson LH, Tamkun MM . Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue . The Journal of Clinical Investigation . 96 . 1 . 282–92 . Jul 1995 . 7615797 . 185199 . 10.1172/JCI118032 .
• Crumb WJ, Wible B, Arnold DJ, Payne JP, Brown AM . Blockade of multiple human cardiac potassium currents by the antihistamine terfenadine: possible mechanism for terfenadine-associated cardiotoxicity . Molecular Pharmacology . 47 . 1 . 181–90 . Jan 1995 . 7838127 .
• Phromchotikul T, Browne DL, Curran ME, Keating MT, Litt M . Dinucleotide repeat polymorphism at the KCNA5 locus . Human Molecular Genetics . 2 . 9 . 1512 . Sep 1993 . 8242092 . 10.1093/hmg/2.9.1512-a .
• Albrecht B, Weber K, Pongs O . Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13 . Receptors & Channels . 3 . 3 . 213–20 . 1996 . 8821794 .
• Holmes TC, Fadool DA, Ren R, Levitan IB . Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain . Science . 274 . 5295 . 2089–91 . Dec 1996 . 8953041 . 10.1126/science.274.5295.2089 . 1996Sci...274.2089H .
• Lacerda AE, Roy ML, Lewis EW, Rampe D . Interactions of the nonsedating antihistamine loratadine with a Kv1.5-type potassium channel cloned from human heart . Molecular Pharmacology . 52 . 2 . 314–22 . Aug 1997 . 9271355 . 10.1124/mol.52.2.314.
• Kääb S, Dixon J, Duc J, Ashen D, Näbauer M, Beuckelmann DJ, Steinbeck G, McKinnon D, Tomaselli GF . Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density . Circulation . 98 . 14 . 1383–93 . Oct 1998 . 9760292 . 10.1161/01.cir.98.14.1383 . free .
• Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D . alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells . FEBS Letters . 473 . 2 . 188–94 . May 2000 . 10812072 . 10.1016/S0014-5793(00)01521-0 . 13026110 . free . 2000FEBSL.473..188M .
• Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A . Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon . The EMBO Journal . 19 . 15 . 4036–45 . Aug 2000 . 10921884 . 306594 . 10.1093/emboj/19.15.4036 .
• Nitabach MN, Llamas DA, Araneda RC, Intile JL, Thompson IJ, Zhou YI, Holmes TC . A mechanism for combinatorial regulation of electrical activity: Potassium channel subunits capable of functioning as Src homology 3-dependent adaptors . Proceedings of the National Academy of Sciences of the United States of America . 98 . 2 . 705–10 . Jan 2001 . 11149959 . 14652 . 10.1073/pnas.031446198 . free .
• Cukovic D, Lu GW, Wible B, Steele DF, Fedida D . A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of alpha-actinin-2 . FEBS Letters . 498 . 1 . 87–92 . Jun 2001 . 11389904 . 10.1016/S0014-5793(01)02505-4 . 20622483 . free . 2001FEBSL.498...87C .
• Kurata HT, Soon GS, Eldstrom JR, Lu GW, Steele DF, Fedida D . Amino-terminal determinants of U-type inactivation of voltage-gated K+ channels . The Journal of Biological Chemistry . 277 . 32 . 29045–53 . Aug 2002 . 12021261 . 10.1074/jbc.M111470200 . free .
• Williams CP, Hu N, Shen W, Mashburn AB, Murray KT . Modulation of the human Kv1.5 channel by protein kinase C activation: role of the Kvbeta1.2 subunit . The Journal of Pharmacology and Experimental Therapeutics . 302 . 2 . 545–50 . Aug 2002 . 12130714 . 10.1124/jpet.102.033357 . 34085749 .
• Eldstrom J, Doerksen KW, Steele DF, Fedida D . N-terminal PDZ-binding domain in Kv1 potassium channels . FEBS Letters . 531 . 3 . 529–37 . Nov 2002 . 12435606 . 10.1016/S0014-5793(02)03572-X . 40689829 . 2002FEBSL.531..529E .
• Zhang S, Kurata HT, Kehl SJ, Fedida D . Rapid induction of P/C-type inactivation is the mechanism for acid-induced K+ current inhibition . The Journal of General Physiology . 121 . 3 . 215–25 . Mar 2003 . 12601085 . 2217332 . 10.1085/jgp.20028760 .

Notes and References

1. Web site: Entrez Gene: KCNA5 potassium voltage-gated channel, shaker-related subfamily, member 5.
2. Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A . Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation . Human Molecular Genetics . 15 . 14 . 2185–91 . Jul 2006 . 16772329 . 10.1093/hmg/ddl143 .
3. Nielsen NH, Winkel BG, Kanters JK, Schmitt N, Hofman-Bang J, Jensen HS, Bentzen BH, Sigurd B, Larsen LA, Andersen PS, Haunsø S, Kjeldsen K, Grunnet M, Christiansen M, Olesen SP . Mutations in the Kv1.5 channel gene KCNA5 in cardiac arrest patients . Biochemical and Biophysical Research Communications . 354 . 3 . 776–82 . Mar 2007 . 17266934 . 10.1016/j.bbrc.2007.01.048 .
4. Eldstrom J, Choi WS, Steele DF, Fedida D . SAP97 increases Kv1.5 currents through an indirect N-terminal mechanism . FEBS Letters . 547 . 1–3 . 205–11 . Jul 2003 . 12860415 . 10.1016/S0014-5793(03)00668-9 . 34857270 . 2003FEBSL.547..205E .
5. Eldstrom J, Doerksen KW, Steele DF, Fedida D . N-terminal PDZ-binding domain in Kv1 potassium channels . FEBS Letters . 531 . 3 . 529–37 . Nov 2002 . 12435606 . 10.1016/S0014-5793(02)03572-X . 40689829 . 2002FEBSL.531..529E .
6. Murata. Mitsunobu. Buckett. Peter D.. Zhou. Jun. Brunner. Michael. Folco. Eduardo. Koren. Gideon. 2001-12-01. SAP97 interacts with Kv1.5 in heterologous expression systems. American Journal of Physiology. Heart and Circulatory Physiology. en. 281. 6. H2575–H2584. 10.1152/ajpheart.2001.281.6.H2575. 11709425. 28915450 . 0363-6135. free.
7. Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D . alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells . FEBS Letters . 473 . 2 . 188–94 . May 2000 . 10812072 . 10.1016/S0014-5793(00)01521-0 . 13026110 . free . 2000FEBSL.473..188M .