K<SUB>v</SUB>1.5 | Voltage-gated potassium channels | IUPHAR/BPS Guide to PHARMACOLOGY

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Target not currently curated in GtoImmuPdb

Target id: 542

Nomenclature: Kv1.5

Family: Voltage-gated potassium channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 613 12p13.3 KCNA5 potassium voltage-gated channel subfamily A member 5 1,6,28
Mouse 6 1 602 6 F3 Kcna5 potassium voltage-gated channel, shaker-related subfamily, member 5
Rat 6 1 602 4q42-44 Kcna5 potassium voltage-gated channel subfamily A member 5
Previous and Unofficial Names
HCK1 | HK2 | HpCN1 | RK3 | RMK2 | potassium voltage-gated channel subfamily A member 5 | RCK7 | RK4 | Potassium (K+) channel protein alpha 5 | potassium channel, voltage gated shaker related subfamily A, member 5 | potassium voltage-gated channel
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
Kv1.2 39
Kv1.3 42
Auxiliary Subunits
Name References
Kvβ1.2 13,39,45
Kvβ2 13,40,45
Kvβ3 18
Other Associated Proteins
Name References
SAP97 25
Src Tyrosine Kinase 14,34
α-actinin 2 (fyn) 21
KChaP (caveolin) 20,46
Kif5b 51
Functional Characteristics
Ion Selectivity and Conductance
Species:  Human
Rank order:  K+ [8.0 pS]
References:  11
Species:  Human
Macroscopic current rectification:  Ik: Delayed Rectifier K+ current
References:  11
Voltage Dependence
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -14.0 - 32 Mouse LTK cell line Mouse
Inactivation  -10.0 260.0 – 5000.0 32
  V0.5 (mV)  τ (msec)  Reference  Cell type  Species 
Activation  -14.0 23.0 11 MEL Human
Inactivation  - - 11
Associated subunits (Human)
Kv β1 and Kv β2

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
dronedarone Hs Inhibition 5.6 pIC50 - - 12
pIC50 5.6 (IC50 2.37x10-6 M) [12]
Description: Whole cell patch clamp experiment using HEK293 cells expressing human Kv1.5.
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Concentration range (M) Holding voltage (mV) Reference
bupivacaine Hs - 5.4 pKd - - 9
pKd 5.4 [9]
quinidine Hs - 5.2 pKd - - 33
pKd 5.2 [33]
resiniferatoxin Hs - 4.6 pKd - - 11
pKd 4.6 [11]
nifedipine Hs - 4.1 pKd - - 11
pKd 4.1 [11]
flecainide Hs - 4.0 pKd - - 11
pKd 4.0 [11]
diltiazem Hs Pore blocker 3.9 pKd - - 11
pKd 3.9 (Kd 1.15x10-4 M) [11]
fampridine Hs Pore blocker 3.6 pKd - - 11
pKd 3.6 (Kd 2.7x10-4 M) [11]
clofilium Hs - 6.9 pIC50 - - 19
pIC50 6.9 [19]
S9947 Hs - 6.4 pIC50 - - 2,16
pIC50 6.4 [2,16]
propafenone Hs - 4.4 pIC50 - - 10
pIC50 4.4 [10]
fampridine N/A - 4.3 pIC50 - - 7
pIC50 4.3 [7]
View species-specific channel blocker tables
Channel Blocker Comments
Kv1.2 and Kv1.5 are resistant to tetraethylammonium [11].
Tissue Distribution
Insulinoma and islet
Species:  Human
Technique:  RT-PCR
References:  15,27
Atrial myocytes, atrium, ventricle
Species:  Human
Technique:  RT-PCR
References:  15,29-30,38,44
Skeletal muscle
Species:  Mouse
Technique:  Northern Blot
References:  22
Pulmonary arterial smooth muscle, spinal cord.
Species:  Rat
Technique:  RT-PCR
References:  24,43,50
Brain: hippocampus, cortex, pituitary, oligodendrocytes, microglia, Schwann cells.
Species:  Rat
Technique:  Immunocytochemistry, RT-PCR, cDNA clone
References:  4,17,35-37
Species:  Rat
Technique:  Northern Blot
References:  22,31
Functional Assays
Molecular clone and voltage clamp
Species:  Human
Tissue:  MEL cells, atrial/ventricular myocytes, mouse L cell line
Response measured:  Ultrarapid-activating K+ current.
References:  8,11,32
Physiological Functions
Maintains membrane potential that modulates electrical excitability in neurons
Species:  Human
Tissue:  Atrial / ventricular myocytes
References:  8,11,32
Kv1.5 has properties similar to the ultrarapidly activating IKur current in the heart. Antisensetargeting Kv1.5 supresses IKur currents by almost 50%.
Species:  Human
Tissue:  Atrial / Ventricular myocytes
References:  8,32
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd
MGI:96662  MP:0000350 abnormal cell proliferation PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd
MGI:96662  MP:0000136 abnormal microglial cell morphology PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd
MGI:96662  MP:0002272 abnormal nervous system electrophysiology PMID: 17055293 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd
MGI:96662  MP:0003957 abnormal nitric oxide homeostasis PMID: 17055293 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6
MGI:96662  MP:0005595 abnormal vascular smooth muscle physiology PMID: 11481235 
Kcna5tm1Hket Kcna5tm1Hket/Kcna5tm1Hket
involves: 129S6/SvEvTac * 129S7/SvEvBrd
MGI:96662  MP:0003488 decreased channel response intensity PMID: 17055293 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6
MGI:96662  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 11349004 
Kcna5tm1(Kcna1)Lndn Kcna5tm1(Kcna1)Lndn/Kcna5tm1(Kcna1)Lndn
involves: C57BL/6
MGI:96662  MP:0003026 decreased vasoconstriction PMID: 11481235 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Atrial fibrillation, familial, 7; ATFB7
Synonyms: Familial atrial fibrillation [Orphanet: ORPHA334] [Disease Ontology: DOID:0050650]
Disease Ontology: DOID:0050650
OMIM: 612240
Orphanet: ORPHA334
Therapeutic use:  Potential use in management of atrial fibrillation, via blockade of IKur
References:  3,41
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human 71-81del Reduced functional expression 47
Missense Human E48G Increased functional expression 5
Missense Human Y155C Reduced functional expression 5
Missense Human A305T Increased functional expression 5
Missense Human D322H Increased functional expression 5
Missense Human D469E Reduced functional expression 5
Missense Human P488S Reduced functional expression 5
Missense Human T527M Reduced functional expression 48
Missense Human A576V Reduced functional expression 48
Missense Human E610K Reduced functional expression 48
Nonsense Human E375X Non-functional 26
Gene Expression and Pathophysiology
Down regulation of mRNA expression and protein synthesis of KCa1.1 and Kv1.5, caused by chronic cigarette smoking
Tissue or cell type:  Bronchial and bronchiolar smooth muscles
Species:  Rat
References:  49
Kv1.5 mRNA levels are dramatically repressed
Tissue or cell type:  Rat hypertrophied ventricles
Pathophysiology:  Altered K+ conductance; possibly responsible for prolonged duration of action potential recorded in hypertrophied ventricles
Species:  Rat
Technique:  RT-PCR, Northern Blotting
References:  23
Expression of Kv1.5 protein reduced by >50% in both the left and the right atrial appendages of AF patients.
Tissue or cell type:  Atrial appendages from patients with AF
Pathophysiology:  Kv1.5 thought to underlie the major component of the ultrarapid delayed rectifier K+ current, IKur
Species:  Human
Technique:  Semi-quantitative PCR, western blotting
References:  41
Biologically Significant Variant Comments
A total of 196 SNPs have been identified in human KCNA5 . For more information see the entry on GeneCards.


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1. Albrecht B, Weber K, Pongs O. (1995) Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13. Recept. Channels, 3 (3): 213-20. [PMID:8821794]

2. Bachmann A, Gutcher I, Kopp K, Brendel J, Bosch RF, Busch AE, Gögelein H. (2001) Characterization of a novel Kv1.5 channel blocker in Xenopus oocytes, CHO cells, human and rat cardiomyocytes. Naunyn Schmiedebergs Arch. Pharmacol., 364 (5): 472-8. [PMID:11692231]

3. Brundel BJ, Van Gelder IC, Henning RH, Tuinenburg AE, Wietses M, Grandjean JG, Wilde AA, Van Gilst WH, Crijns HJ. (2001) Alterations in potassium channel gene expression in atria of patients with persistent and paroxysmal atrial fibrillation: differential regulation of protein and mRNA levels for K+ channels. J. Am. Coll. Cardiol., 37 (3): 926-32. [PMID:11693772]

4. Chittajallu R, Chen Y, Wang H, Yuan X, Ghiani CA, Heckman T, McBain CJ, Gallo V. (2002) Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle. Proc. Natl. Acad. Sci. U.S.A., 99 (4): 2350-5. [PMID:11854528]

5. Christophersen IE, Olesen MS, Liang B, Andersen MN, Larsen AP, Nielsen JB, Haunsø S, Olesen SP, Tveit A, Svendsen JH et al.. (2013) Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur. Heart J., 34 (20): 1517-25. [PMID:23264583]

6. Curran ME, Landes GM, Keating MT. (1992) Molecular cloning, characterization, and genomic localization of a human potassium channel gene. Genomics, 12 (4): 729-37. [PMID:1349297]

7. Fedida D, Wible B, Wang Z, Fermini B, Faust F, Nattel S, Brown AM. (1993) Identity of a novel delayed rectifier current from human heart with a cloned K+ channel current. Circ. Res., 73 (1): 210-6. [PMID:8508531]

8. Feng J, Wible B, Li GR, Wang Z, Nattel S. (1997) Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes. Circ. Res., 80 (4): 572-9. [PMID:9118489]

9. Franqueza L, Longobardo M, Vicente J, Delpón E, Tamkun MM, Tamargo J, Snyders DJ, Valenzuela C. (1997) Molecular determinants of stereoselective bupivacaine block of hKv1.5 channels. Circ. Res., 81 (6): 1053-64. [PMID:9400387]

10. Franqueza L, Valenzuela C, Delpón E, Longobardo M, Caballero R, Tamargo J. (1998) Effects of propafenone and 5-hydroxy-propafenone on hKv1.5 channels. Br. J. Pharmacol., 125 (5): 969-78. [PMID:9846634]

11. Grissmer S, Nguyen AN, Aiyar J, Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG. (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol., 45 (6): 1227-34. [PMID:7517498]

12. Guo X, Ma X, Yang Q, Xu J, Huang L, Jia J, Shan J, Liu L, Chen W, Chu H et al.. (2014) Discovery of 1-aryloxyethyl piperazine derivatives as Kv1.5 potassium channel inhibitors (part I). Eur J Med Chem, 81: 89-94. [PMID:24824064]

13. Heinemann SH, Rettig J, Graack HR, Pongs O. (1996) Functional characterization of Kv channel beta-subunits from rat brain. J. Physiol. (Lond.), 493 ( Pt 3): 625-33. [PMID:8799886]

14. Holmes TC, Fadool DA, Ren R, Levitan IB. (1996) Association of Src tyrosine kinase with a human potassium channel mediated by SH3 domain. Science, 274 (5295): 2089-91. [PMID:8953041]

15. Kamb A, Weir M, Rudy B, Varmus H, Kenyon C. (1989) Identification of genes from pattern formation, tyrosine kinase, and potassium channel families by DNA amplification. Proc. Natl. Acad. Sci. U.S.A., 86 (12): 4372-6. [PMID:2734290]

16. Knobloch K, Brendel J, Peukert S, Rosenstein B, Busch AE, Wirth KJ. (2002) Electrophysiological and antiarrhythmic effects of the novel I(Kur) channel blockers, S9947 and S20951, on left vs. right pig atrium in vivo in comparison with the I(Kr) blockers dofetilide, azimilide, d,l-sotalol and ibutilide. Naunyn Schmiedebergs Arch. Pharmacol., 366 (5): 482-7. [PMID:12382079]

17. Kotecha SA, Schlichter LC. (1999) A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation. J. Neurosci., 19 (24): 10680-93. [PMID:10594052]

18. Leicher T, Bähring R, Isbrandt D, Pongs O. (1998) Coexpression of the KCNA3B gene product with Kv1.5 leads to a novel A-type potassium channel. J. Biol. Chem., 273 (52): 35095-101. [PMID:9857044]

19. Malayev AA, Nelson DJ, Philipson LH. (1995) Mechanism of clofilium block of the human Kv1.5 delayed rectifier potassium channel. Mol. Pharmacol., 47 (1): 198-205. [PMID:7838129]

20. Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM. (2001) Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J. Biol. Chem., 276 (11): 8409-14. [PMID:11115511]

21. Maruoka ND, Steele DF, Au BP, Dan P, Zhang X, Moore ED, Fedida D. (2000) alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS Lett., 473 (2): 188-94. [PMID:10812072]

22. Matsubara H, Liman ER, Hess P, Koren G. (1991) Pretranslational mechanisms determine the type of potassium channels expressed in the rat skeletal and cardiac muscles. J. Biol. Chem., 266 (20): 13324-8. [PMID:1712780]

23. Matsubara H, Suzuki J, Inada M. (1993) Shaker-related potassium channel, Kv1.4, mRNA regulation in cultured rat heart myocytes and differential expression of Kv1.4 and Kv1.5 genes in myocardial development and hypertrophy. J. Clin. Invest., 92 (4): 1659-66. [PMID:7691883]

24. Matus-Leibovitch N, Vogel Z, Ezra-Macabee V, Etkin S, Nevo I, Attali B. (1996) Chronic morphine administration enhances the expression of Kv1.5 and Kv1.6 voltage-gated K+ channels in rat spinal cord. Brain Res. Mol. Brain Res., 40 (2): 261-70. [PMID:8872310]

25. Murata M, Buckett PD, Zhou J, Brunner M, Folco E, Koren G. (2001) SAP97 interacts with Kv1.5 in heterologous expression systems. Am. J. Physiol. Heart Circ. Physiol., 281 (6): H2575-84. [PMID:11709425]

26. Olson TM, Alekseev AE, Liu XK, Park S, Zingman LV, Bienengraeber M, Sattiraju S, Ballew JD, Jahangir A, Terzic A. (2006) Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum. Mol. Genet., 15 (14): 2185-91. [PMID:16772329]

27. Philipson LH, Hice RE, Schaefer K, LaMendola J, Bell GI, Nelson DJ, Steiner DF. (1991) Sequence and functional expression in Xenopus oocytes of a human insulinoma and islet potassium channel. Proc. Natl. Acad. Sci. U.S.A., 88 (1): 53-7. [PMID:1986382]

28. Phromchotikul T, Browne DL, Curran ME, Keating MT, Litt M. (1993) Dinucleotide repeat polymorphism at the KCNA5 locus. Hum. Mol. Genet., 2 (9): 1512. [PMID:8242092]

29. Ramaswami M, Gautam M, Kamb A, Rudy B, Tanouye MA, Mathew MK. (1990) Human potassium channel genes: Molecular cloning and functional expression. Mol. Cell. Neurosci., 1 (3): 214-23. [PMID:19912772]

30. Rampe D, Wang Z, Fermini B, Wible B, Dage RC, Nattel S. (1995) Voltage- and time-dependent block by perhexiline of K+ currents in human atrium and in cells expressing a Kv1.5-type cloned channel. J. Pharmacol. Exp. Ther., 274 (1): 444-9. [PMID:7616429]

31. Roberds SL, Tamkun MM. (1991) Cloning and tissue-specific expression of five voltage-gated potassium channel cDNAs expressed in rat heart. Proc. Natl. Acad. Sci. U.S.A., 88 (5): 1798-802. [PMID:1705709]

32. Snyders DJ, Tamkun MM, Bennett PB. (1993) A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J. Gen. Physiol., 101 (4): 513-43. [PMID:8505626]

33. Snyders J, Knoth KM, Roberds SL, Tamkun MM. (1992) Time-, voltage-, and state-dependent block by quinidine of a cloned human cardiac potassium channel. Mol. Pharmacol., 41 (2): 322-30. [PMID:1538710]

34. Sobko A, Peretz A, Attali B. (1998) Constitutive activation of delayed-rectifier potassium channels by a src family tyrosine kinase in Schwann cells. EMBO J., 17 (16): 4723-34. [PMID:9707431]

35. Sobko A, Peretz A, Shirihai O, Etkin S, Cherepanova V, Dagan D, Attali B. (1998) Heteromultimeric delayed-rectifier K+ channels in schwann cells: developmental expression and role in cell proliferation. J. Neurosci., 18 (24): 10398-408. [PMID:9852577]

36. Swanson R, Marshall J, Smith JS, Williams JB, Boyle MB, Folander K, Luneau CJ, Antanavage J, Oliva C, Buhrow SA. (1990) Cloning and expression of cDNA and genomic clones encoding three delayed rectifier potassium channels in rat brain. Neuron, 4 (6): 929-39. [PMID:2361015]

37. Takimoto K, Fomina AF, Gealy R, Trimmer JS, Levitan ES. (1993) Dexamethasone rapidly induces Kv1.5 K+ channel gene transcription and expression in clonal pituitary cells. Neuron, 11 (2): 359-69. [PMID:8352944]

38. Tamkun MM, Knoth KM, Walbridge JA, Kroemer H, Roden DM, Glover DM. (1991) Molecular cloning and characterization of two voltage-gated K+ channel cDNAs from human ventricle. FASEB J., 5 (3): 331-7. [PMID:2001794]

39. Thorneloe KS, Chen TT, Kerr PM, Grier EF, Horowitz B, Cole WC, Walsh MP. (2001) Molecular composition of 4-aminopyridine-sensitive voltage-gated K(+) channels of vascular smooth muscle. Circ. Res., 89 (11): 1030-7. [PMID:11717160]

40. Uebele VN, England SK, Chaudhary A, Tamkun MM, Snyders DJ. (1996) Functional differences in Kv1.5 currents expressed in mammalian cell lines are due to the presence of endogenous Kv beta 2.1 subunits. J. Biol. Chem., 271 (5): 2406-12. [PMID:8576199]

41. Van Wagoner DR, Pond AL, McCarthy PM, Trimmer JS, Nerbonne JM. (1997) Outward K+ current densities and Kv1.5 expression are reduced in chronic human atrial fibrillation. Circ. Res., 80 (6): 772-81. [PMID:9168779]

42. Vicente R, Escalada A, Villalonga N, Texidó L, Roura-Ferrer M, Martín-Satué M, López-Iglesias C, Soler C, Solsona C, Tamkun MM et al.. (2006) Association of Kv1.5 and Kv1.3 contributes to the major voltage-dependent K+ channel in macrophages. J. Biol. Chem., 281 (49): 37675-85. [PMID:17038323]

43. Wang J, Juhaszova M, Rubin LJ, Yuan XJ. (1997) Hypoxia inhibits gene expression of voltage-gated K+ channel alpha subunits in pulmonary artery smooth muscle cells. J. Clin. Invest., 100 (9): 2347-53. [PMID:9410914]

44. Wang Z, Fermini B, Nattel S. (1993) Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents. Circ. Res., 73 (6): 1061-76. [PMID:8222078]

45. Wang Z, Kiehn J, Yang Q, Brown AM, Wible BA. (1996) Comparison of binding and block produced by alternatively spliced Kvbeta1 subunits. J. Biol. Chem., 271 (45): 28311-7. [PMID:8910452]

46. Wible BA, Yang Q, Kuryshev YA, Accili EA, Brown AM. (1998) Cloning and expression of a novel K+ channel regulatory protein, KChAP. J. Biol. Chem., 273 (19): 11745-51. [PMID:9565597]

47. Yang T, Yang P, Roden DM, Darbar D. (2010) Novel KCNA5 mutation implicates tyrosine kinase signaling in human atrial fibrillation. Heart Rhythm, 7 (9): 1246-52. [PMID:20638934]

48. Yang Y, Li J, Lin X, Yang Y, Hong K, Wang L, Liu J, Li L, Yan D, Liang D et al.. (2009) Novel KCNA5 loss-of-function mutations responsible for atrial fibrillation. J. Hum. Genet., 54 (5): 277-83. [PMID:19343045]

49. Ye H, Ma WL, Yang ML, Liu SY, Wang DX. (2004) Effect of chronic cigarette smoking on large-conductance calcium-activated potassium channel and Kv1.5 expression in bronchial smooth muscle cells of rats. Sheng li xue bao : [Acta physiologica Sinica], 56 (5): 573-8. [PMID:15497036]

50. Yuan XJ, Wang J, Juhaszova M, Golovina VA, Rubin LJ. (1998) Molecular basis and function of voltage-gated K+ channels in pulmonary arterial smooth muscle cells. Am. J. Physiol., 274 (4 Pt 1): L621-35. [PMID:9575881]

51. Zadeh AD, Cheng Y, Xu H, Wong N, Wang Z, Goonasekara C, Steele DF, Fedida D. (2009) Kif5b is an essential forward trafficking motor for the Kv1.5 cardiac potassium channel. J. Physiol. (Lond.), 587 (Pt 19): 4565-74. [PMID:19675065]


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