Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes – shaker, shaw, shab, and shal – have been identified in Drosophila, and each has been shown to have human homolog(s).
Kv4.3 is a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene.
Gain of function is believed to cause Brugada Syndrome although only indirectly shown by mutations in the beta subunit KCNE3 which causes gain of function of Kv4.3.
^Postma AV, Bezzina CR, de Vries JF, Wilde AA, Moorman AF, Mannens MM (Aug 2000). "Genomic organisation and chromosomal localisation of two members of the KCND ion channel family, KCND2 and KCND3". Hum Genet. 106 (6): 614–9. doi:10.1007/s004390050033. PMID10942109.
^Gutman GA, Chandy KG, Grissmer S, Lazdunski M, McKinnon D, Pardo LA, Robertson GA, Rudy B, Sanguinetti MC, Stuhmer W, Wang X (Dec 2005). "International Union of Pharmacology. LIII. Nomenclature and molecular relationships of voltage-gated potassium channels". Pharmacol Rev. 57 (4): 473–508. doi:10.1124/pr.57.4.10. PMID16382104.
^Oudit GY, Kassiri Z, Sah R, Ramirez RJ, Zobel C, Backx PH (May 2001). "The molecular physiology of the cardiac transient outward potassium current (I(to)) in normal and diseased myocardium". J. Mol. Cell. Cardiol. 33 (5): 851–72. doi:10.1006/jmcc.2001.1376. PMID11343410.
Serôdio P, Vega-Saenz de Miera E, Rudy B (1997). "Cloning of a novel component of A-type K+ channels operating at subthreshold potentials with unique expression in heart and brain". J. Neurophysiol. 75 (5): 2174–9. doi:10.1152/jn.19220.127.116.114. PMID8734615.
Kong W, Po S, Yamagishi T, et al. (1999). "Isolation and characterization of the human gene encoding Ito: further diversity by alternative mRNA splicing". Am. J. Physiol. 275 (6 Pt 2): H1963–70. PMID9843794.
Ren X, Shand SH, Takimoto K (2003). "Effective association of Kv channel-interacting proteins with Kv4 channel is mediated with their unique core peptide". J. Biol. Chem. 278 (44): 43564–70. doi:10.1074/jbc.M302337200. PMID12928444.
Hatano N, Ohya S, Muraki K, et al. (2004). "Two arginines in the cytoplasmic C-terminal domain are essential for voltage-dependent regulation of A-type K+ current in the Kv4 channel subfamily". J. Biol. Chem. 279 (7): 5450–9. doi:10.1074/jbc.M302034200. PMID14645239.
Frank-Hansen R, Larsen LA, Andersen P, et al. (2005). "Mutations in the genes KCND2 and KCND3 encoding the ion channels Kv4.2 and Kv4.3, conducting the cardiac fast transient outward current (ITO,f), are not a frequent cause of long QT syndrome". Clin. Chim. Acta. 351 (1–2): 95–100. doi:10.1016/j.cccn.2004.08.017. PMID15563876.
Baltaev R, Strutz-Seebohm N, Korniychuk G, et al. (2005). "Regulation of cardiac shal-related potassium channel Kv 4.3 by serum- and glucocorticoid-inducible kinase isoforms in Xenopus oocytes". Pflügers Arch. 450 (1): 26–33. doi:10.1007/s00424-004-1369-z. PMID15578212.
Potapova IA, Cohen IS, Doronin SV (2007). "Voltage-gated ion channel Kv4.3 is associated with Rap guanine nucleotide exchange factors and regulates angiotensin receptor type 1 signaling to small G-protein Rap". FEBS J. 274 (17): 4375–84. doi:10.1111/j.1742-4658.2007.05966.x. PMID17725712.