K v7 positive modulators reduce detrusor overactivity and increase bladder capacity in rats

Basic and Clinical Pharmacology and Toxicology

Volumn 110, Issue 2, 2012, Pages 145-153

  Svalø, Julie ^a,b   Hansen, Henrik H ^a   Rønn, Lars Christian B ^a   Sheykhzade, Majid ^b   Munro, Gordon ^a   Rode, Frederik ^a  

^a NEUROSEARCH A S   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; CAPSAICIN; MESSENGER RNA; POTASSIUM CHANNEL KCNQ1; POTASSIUM CHANNEL KCNQ4; POTASSIUM CHANNEL KCNQ5; RETIGABINE; 10,10-BIS(4-PYRIDINYLMETHYL)-9(10H)-ANTHRACENONE; ANTHRACENE DERIVATIVE; CARBAMIC ACID DERIVATIVE; PHENYLENEDIAMINE DERIVATIVE; POTASSIUM CHANNEL KCNQ;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLADDER CAPACITY; BLADDER CONTRACTION; BLADDER FUNCTION; CONTROLLED STUDY; CYSTOMETRY; DRUG EFFECT; FEMALE; MICTURITION; NONHUMAN; OVERACTIVE BLADDER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; RAT; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA TRANSCRIPTION; WESTERN BLOTTING; ANIMAL; BLADDER; DRUG EFFECTS; GENETICS; METABOLISM; SPRAGUE DAWLEY RAT; URINARY BLADDER, OVERACTIVE;

RATTUS;

ANIMALS; ANTHRACENES; CAPSAICIN; CARBAMATES; FEMALE; KCNQ POTASSIUM CHANNELS; PHENYLENEDIAMINES; RATS; RATS, SPRAGUE-DAWLEY; RNA, MESSENGER; URINARY BLADDER; URINARY BLADDER, OVERACTIVE;

EID: 84855945645     PISSN: 17427835     EISSN: 17427843     Source Type: Journal    
DOI: 10.1111/j.1742-7843.2011.00765.x     Document Type: Article

References (43)

1. Irwin DE, Milsom I, Hunskaar S, Reilly K, Kopp Z, Herschorn S et al. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC Study. Eur Urol 2006;50:1306-15.
2. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci 2008;9:453-66.
3. Sellers DJ, McKay N. Developments in the pharmacotherapy of the overactive bladder. Curr Opin Urol 2007;17:223-30.
4. Andersson KE. LUTS treatment: future treatment options. Neurourol Urodyn 2007;26:934-47.
5. Colli E, Digesu GA, Olivieri L. Overactive bladder treatments in early phase clinical trials. Expert Opin Investig Drugs 2007;16:999-1007.
6. Gan XG, An RH, Bai YF, Zong DB. Expressions of voltage-gated K+ channel 2.1 and 2.2 in rat bladder with detrusor hyperreflexia. Chin Med J (Engl) 2008;121:1574-7.
7. Steers WD, Tuttle JB. Role of ion channels in bladder function and voiding disorders. Curr bladder dysfunct repo 2009;4:125-31.
8. Robbins J. KCNQ potassium channels: physiology, pathophysiology, and pharmacology. Pharmacol Ther 2001;90:1-9.
9. Joshi S, Balan P, Gurney AM. Pulmonary vasoconstrictor action of KCNQ potassium channel blockers. Respir Res 2006;7:31.
10. McCallum LA, Pierce SL, England SK, Greenwood IA, Tribe RM. The contribution of Kv7 channels to pregnant mouse and human myometrial contractility. J Cell Mol Med 2010;15:577-86.
11. Schenzer A, Friedrich T, Pusch M, Saftig P, Jentsch TJ, Grötzinger J et al. Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine. J Neurosci 2005;25:5051-60.
12. Tatulian L, Delmas P, Abogadie FC, Brown DA. Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine. J Neurosci 2001;21:5535-45.
13. Wuttke TV, Seebohm G, Bail S, Maljevic S, Lerche H. The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol 2005;67:1009-17.
14. Streng T, Christoph T, Andersson KE. Urodynamic effects of the K+ channel (KCNQ) opener retigabine in freely moving, conscious rats. J Urol 2004;172:2054-8.
15. Anderson UA, Carson C, McCloskey KD. KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder. J Urol 2009;182:330-6.
16. Rode F, Svalø J, Sheykhzade M, Rønn LCB. Functional effects of the KCNQ modulators retigabine and XE991 in the rat urinary bladder. Eur J Pharmacol 2010;638:121-7.
17. Hougaard C, Fraser MO, Chien C, Bookout A, Katofiasc M, Jensen BS et al. A positive modulator of K Ca 2 and K Ca 3 channels, 4, 5-dichloro-1, 3-diethyl-1, 3-dihydro-benzoimidazol-2-one (NS4591), inhibits bladder afferent firing in vitro and bladder overactivity in vivo. J Pharmacol Exp Ther 2009;328:28-39.
18. Ning Lo W, Liang W. Blockade of voltage-sensitive K(+) channels increases contractility more in transverse than in longitudinal rat detrusor Strips. Urology 2008;10:R115.
19. Fry CH, Daneshgari F, Thor K, Drake M, Eccles R, Kanai AJ et al. Animal models and their use in understanding lower urinary tract dysfunction. Neurourol Urodyn 2010;29:603-8.
20. Kakizaki H, de Groat WC. Role of spinal nitric oxide in the facilitation of the micturition reflex by bladder irritation. J Urol 1996;155:355-60.
21. Mitsui T, Kakizaki H, Matsuura S, Ameda K, Yoshioka M, Koyanagi T et al. Afferent fibers of the hypogastric nerves are involved in the facilitating effects of chemical bladder irritation in rats. J Neurophysiol 2001;86:2276-84.
22. Nishijima S, Sugaya K, Kadekawa K, Naka H, Miyazato M. Comparison of the effect of anti-muscarinic agents on bladder activity, urinary ATP level, and autonomic nervous system in rats. Biomed Res 2009;30:107-12.
23. Woods M, Carson N, Norton NW, Sheldon JH, Argentieri TM. Efficacy of the beta3-adrenergic receptor agonist CL-316243 on experimental bladder hyperreflexia and detrusor instability in the rat. J Urol 2001;166:1142-7.
24. Nagabukuro H, Degenhardt A, Villa KL, Mistry SL, Gichuru L, Jochnowitz N et al. Correlation between pharmacologically-induced changes in cystometric parameters and spinal c-Fos expression in rats. Auton Neurosci 2010;156:19-26.
25. Avelino A, Cruz F. TRPV1 (vanilloid receptor) in the urinary tract: expression, function and clinical applications. Naunyn Schmiedebergs Arch Pharmacol 2006;373:287-99.
26. Brady CM, Apostolidis AN, Harper M, Yiangou Y, Beckett A, Jacques TS et al. Parallel changes in bladder suburothelial vanilloid receptor TRPV1 and pan-neuronal marker PGP9.5 immunoreactivity in patients with neurogenic detrusor overactivity after intravesical resiniferatoxin treatment. BJU Int 2004;93:770-6.
27. Yeung S, Schwake M, Pucovský V, Greenwood I. Bimodal effects of the Kv7 channel activator retigabine on vascular K+ currents. Br J Pharmacol 2008;155:62-72.
28. Yeung SYM, Greenwood IA. Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells. Br J Pharmacol 2005;146:585-95.
29. Hernandez CC, Zaika O, Tolstykh GP, Shapiro MS. Regulation of neural KCNQ channels: signalling pathways, structural motifs and functional implications. J Physiol 2008;586:1811-21.
30. Ohya S, Asakura K, Muraki K, Watanabe M, Imaizumi Y. Molecular and functional characterization of ERG, KCNQ, and KCNE subtypes in rat stomach smooth muscle. Am J Physiol Gastrointest Liver Physiol 2002;282:G277-87.
31. Brueggemann LI, Moran CJ, Barakat JA, Yeh JZ, Cribbs LL, Byron KL et al. Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells. Am J Physiol Heart Circ Physiol 2007;292:H1352-63.
32. Mackie AR, Brueggemann LI, Henderson KK, Shiels AJ, Cribbs LL, Scrogin KE et al. Vascular KCNQ potassium channels as novel targets for the control of mesenteric artery constriction by vasopressin, based on studies in single cells, pressurized arteries, and in vivo measurements of mesenteric vascular resistance. J Pharmacol Exp Ther 2008;325:475-83.
33. Yeung SYM, Pucovský V, Moffatt JD, Saldanha L, Schwake M, Ohya S et al. Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity. Br J Pharmacol 2007;151:758-70.
34. Ng FL, Davis AJ, Jepps TA, Harhun MI, Yeung SY, Wan A et al. Expression and function of the K+ channel KCNQ genes in human arteries. Br J Pharmacol 2011;162:42-53.
35. Joshi S, Sedivy V, Hodyc D, Herget J, Gurney AM. KCNQ modulators reveal a key role for KCNQ potassium channels in regulating the tone of rat pulmonary artery smooth muscle. J Pharmacol Exp Ther 2009;329:368-76.
36. McCallum LA, Greenwood IA, Tribe RM. Expression and function of K(v)7 channels in murine myometrium throughout oestrous cycle. Pflugers Arch 2009;457:1111-20.
37. Jepps TA, Greenwood IA, Moffatt JD, Sanders KM, Ohya S. Molecular and functional characterization of Kv7K+ channel in murine gastrointestinal smooth muscles. Am J Physiol Gastrointest Liver Physiol 2009;297:G107-15.
38. Kubisch C, Schroeder BC, Friedrich T, Lütjohann B, El-Amraoui A, Marlin S et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 1999;96:437-46.
39. Bal M, Zhang J, Zaika O, Hernandez CC, Shapiro MS. Homomeric and heteromeric assembly of KCNQ (Kv7) K+ channels assayed by total internal reflection fluorescence/fluorescence resonance energy transfer and patch clamp analysis. J Biol Chem 2008;283:30668-76.
40. Valeant Pharmaceuticals North America. Ezogabine for Partial Seizures in Epilepsy (NDA - 022345) [Internet]. [cited 2011]. Available from: 2010 (last accessed on 3 January 2011).
41. Bialer M, Johannessen SI, Levy RH, Perucca E, Tomson T, White HS et al. Progress report on new antiepileptic drugs: a summary of the Ninth Eilat Conference (EILAT IX). Epilepsy Res 2009;83:1-43.
42. Hiller A, Nguyen N, Strassburg CP, Li Q, Jainta H, Pechstein B et al. Retigabine N-glucuronidation and its potential role in enterohepatic circulation. Drug Metab Dispos 1999;27:605-12.
43. Mackie AR, Byron KL. Cardiovascular KCNQ (Kv7) potassium channels: physiological regulators and new targets for therapeutic intervention. Mol Pharmacol 2008;74:1171-9.