TABLE 5

KV1.4 channels

Channel name KV1.41,2,3,4,5,6,7
Description Voltage-gated potassium channel, A-type, fast-inactivating
Other names HuK (II), hPCN2, HK1, RCK4, RHK1, RK4, RK8, MK4
Molecular information Human: 653aa, NM_002233, chr. 11p14.3–15.2,7 KCNA4, GeneID: 3739, PMID: 226348932
Mouse: 654aa, NM_021275, chr. 2
Rat: 654aa, NM_012971, chr. 3q33
Associated subunits KVβ, PSD95, synapse-associated protein 97 (SAP97), SAP90, α-actinin-2, KChaP, σ receptor8,9,10,11,12,13,14,15,16,17,18
Functional assays Voltage-clamp
Current KV1.4/KV1.2 heteromultimers may underlie the presynaptic A-type K+ channel19
Conductance 5pS1
Ion selectivity K+-selective (50 times more selective for K+ than Na+)20
Activation Voltage, Va = -22 mV1; -34 mV20; Ka = 521
Inactivation N-type inactivation, Vh = -62 mV20; τh = 47 ms (0 mV)20
Activators CaMKII/calcineurin regulation through phosphorylation/dephosphorylation makes inactivation Ca2+-dependent22
Gating inhibitors None
Blockers 4-Aminopyridine (13 μM),1 tetraethyammonium (>100 mM),3 UK78282 (170 nM),23 riluzole (70 μM),24 quinidine (10 μM-1 mM),25 nicardipine (0.8 μM)26
Radioligands None
Channel distribution Brain (olfactory bulb, corpus striatum > hippocampus, superior and inferior colliculus > cerebral cortex, midbrain basal ganglia > pons/medulla), lung-carcinoid, skeletal muscle, heart, pancreatic islet1,6,27,28,29
Physiological functions Neuronal afterhypolarization
Mutations and pathophysiology KV1.4 expression increases in rat ventricular myocytes after myocardial infarction and induction of diabetes30,31
Pharmacological significance Not established
Comments Can coassemble with other Kv1 family members in heteromultimers but not with members of other Kv families; intronless coding region; mouse Kv1.4 mRNA contains an internal ribosome entry site in its 5′-noncoding region and may be translated by cap-independent mechanisms33,34; mammalian Shaker-related family

  • aa, amino acids; chr., chromosome.

  • ↵1. Stuhmer W, Ruppersberg JP, Schroter KH, Sakmann B, Stocker M, Giese KP, Perschke A, Baumann A, and Pongs O (1989) Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J 8:3235-3244

  • ↵2. Kamb A, Weir M, Rudy B, Varmus H, and Kenyon C (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. Proc Natl Acad Sci USA 86:4372-4376

  • ↵3. Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, and Steiner DF (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc Natl Acad Sci USA 88:53-57

  • ↵4. Tseng-Crank JC, Tseng GN, Schwartz A, and Tanouye MA (1990) Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library. FEBS Lett 268:63-68

  • ↵5. Roberds SL and Tamkun MM (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc Natl Acad Sci USA 88:1798-1802

  • ↵6. Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, and Glover DM (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J 5:331-337

  • ↵7. Wymore RS, Korenberg JR, Kinoshita KD, Aiyar J, Coyne C, Chen XN, Hustad CM, Copeland NG, Gutman GA, Jenkins NA, et al. (1994) Genomic organization, nucleotide sequence, biophysical properties, and localization of the voltage-gated K+ channel gene KCNA4/Kv1.4 to mouse chromosome 2/human 11p14 and mapping of KCNC1/Kv3.1 to mouse 7/human11p14.3-p15.2 and KCNA1/Kv1.1 to human 12p13. Genomics 20:191-202

  • ↵8. Morales MJ, Castellino RC, Crews AL, Rasmusson RL, and Strauss HC (1995) A novel β subunit increases rate of inactivation of specific voltage-gated potassium channel α subunits. J Biol Chem 270:6272-6277

  • ↵9. Rhodes KJ, Keilbaugh SA, Barrezueta NX, Lopez KL, and Trimmer JS (1995) Association and colocalization of K+ channel α- and β-subunit polypeptides in rat brain. J Neurosci 15:5360-5371

  • ↵10. McCormack K, McCormack T, Tanouye M, Rudy B, and Stuhmer W (1995) Alternative splicing of the human Shaker K+ channel β 1 gene and functional expression of the β 2 gene product. FEBS Lett 370:32-36

  • ↵11. Heinemann SH, Rettig J, Graack HR, and Pongs O (1996) Functional characterization of Kv channel β-subunits from rat brain. J Physiol 493:625-633

  • ↵12. Rhodes KJ, Strassle BW, Monaghan MM, Bekele-Arcuri Z, Matos MF, and Trimmer JS (1997) Association and colocalization of the Kvβ1 and Kvβ2 β-subunits with Kv1 α-subunits in mammalian brain K+ channel complexes. J Neurosci 17:8246-8258

  • ↵13. Kim E and Sheng M (1996) Differential K+ channel clustering activity of PSD-95 and SAP97, two related membrane-associated putative guanylate kinases. Neuropharmacology 35:993-1000

  • ↵14. Topinka JR and Bredt DS (1998) N-terminal palmitoylation of PSD-95 regulates association with cell membranes and interaction with K+ channel Kv1.4. Neuron 20:125-134

  • ↵15. Cukovic D, Lu GW, Wible B, Steele DF, and Fedida D (2001) A discrete amino terminal domain of Kv1.5 and Kv1.4 potassium channels interacts with the spectrin repeats of α-actinin-2. FEBS Lett 498:87-92

  • ↵16. Kuryshev YA, Wible BA, Gudz TI, Ramirez AN, and Brown AM (2001) KChAP/Kvβ1.2 interactions and their effects on cardiac Kv channel expression. Am J Physiol Cell Physiol 281:C290-C299

  • ↵17. Piserchio A, Pellegrini M, Mehta S, Blackman SM, Garcia EP, Marshall J, and Mierke DF (2002) The PDZ1 domain of SAP90: characterization of structure and binding. J Biol Chem 277:6967-6973

  • ↵18. Aydar E, Palmer CP, Klyachko VA, and Jackson MB (2002) The sigma receptor as a ligand-regulated auxiliary potassium channel subunit. Neuron 34:399-410

  • ↵19. Sheng M, Liao YJ, Jan YN, and Jan LY (1993) Presynaptic A-current based on heteromultimeric K+ channels detected in vivo. Nature (Lond) 365:72-75

  • ↵20. Po S, Snyders DJ, Baker R, Tamkun MM, and Bennett PB (1992) Functional expression of an inactivating potassium channel cloned from human heart. Circ Res 71:732-736

  • ↵21. Elliott A and Elliott JR (1997) Channel-specific effects of n-alkyl sulphate anions on three Shaker-related potassium channels expressed in Xenopus oocytes. Pflueg Arch Eur J Physiol 434:132-136

  • ↵22. Roeper J, Lorra C, and Pongs O (1997) Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase. J Neurosci 17:3379-3391

  • ↵23. Nguyen A, Kath JC, Hanson DC, Biggers MS, Canniff PC, Donovan CB, Mather RJ, Bruns MJ, Rauer H, Aiyar J, et al (1996) Novel non peptide agents potently block the C-type inactivated conformation of Kv1.3 and suppress T cell activation. Mol Pharmacol 50:1672-1679

  • ↵24. Xu L, Enyeart JA, and Enyeart JJ (2001) Neuro protective agent riluzole dramatically slows in-activation of Kv1.4 potassium channels by a voltage-dependent oxidative mechanism. J Pharmacol Exp Ther 299:227-237

  • ↵25. Yamagishi T, Ishii K, and Taira N (1995) Antiarrhythmic and bradycardic drugs inhibit currents of cloned K+ channels, KV1.2 and KV1.4. Eur J Pharmacol 281:151-159

  • ↵26. Hatano N, Ohya S, Muraki K, Giles W, and Imaizumi Y (2003) Dihydropyridine Ca2+ channel antagonists and agonists block Kv4.2, Kv4.3 and Kv1.4 K+ channels expressed in HEK293 cells. Br J Pharmacol 139:533-544

  • ↵27. Beckh S and Pongs O (1990) Members of the RCK potassium channel family are differentially expressed in the rat nervous system. EMBO J 9:777-782

  • ↵28. Sheng M, Tsaur ML, Jan YN, and Jan LY (1992) Subcellular segregation of two A-type K+ channel proteins in rat central neurons. Neuron 9:271-284

  • ↵29. Blair TA, Roberds SL, Tamkun MM, and Hartshorne RP (1991) Functional characterization of RK5, a voltage-gated K+ channel cloned from the rat cardiovascular system. FEBS Lett 295:211-213

  • ↵30. Kaprielian R, Wickenden AD, Kassiri Z, Parker TG, Liu PP, and Backx, PH (1999) Relationship between K+ channel down-regulation and [Ca2+]i in rat ventricular myocytes following myocardial infarction. J Physiol (Lond) 517:229-245

  • ↵31. Nishiyama A, Ishii DN, Backx PH, Pulford BE, Birks BR, and Tamkun MM (2001) Altered K+ channel gene expression in diabetic rat ventricle: isoform switching between Kv4.2 and Kv1.4. Am J Physiol 281:H1800-H1807

  • ↵32. Philipson LH, Schaefer K, LaMendola J, Bell GI, and Steiner DF (1990) Sequence of a human fetal skeletal muscle potassium channel cDNA related to RCK4. Nucleic Acids Res 18:7160

  • ↵33. Negulescu D, Long LE, Chandy KG, Semler B, and Gutman GA (1998) Translation initiation of a cardiac voltage-gated potassium channel by internal ribosome entry. J Biol Chem 273:20109-20113

  • ↵34. Jang GM, Leong LE, Hoang LT, Wang PH, Gutman GA, Semler BL (2004) Structurally distinct elements mediate internal ribosome entry within the 5′ noncoding region of a voltage-gated potassium channel mRNA. J Biol Chem 279:47419-47430