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Literature DB >> 22880633

One man's side effect is another man's therapeutic opportunity: targeting Kv7 channels in smooth muscle disorders.

Abstract

Retigabine is a first in class anticonvulsant that has recently undergone clinical trials to test its efficacy in epileptic patients. Retigabine's novel mechanism of action - activating Kv7 channels - suppresses neuronal activity to prevent seizure generation by hyperpolarizing the membrane potential and suppressing depolarizing surges. However, Kv7 channels are not expressed exclusively in neurones and data generated over the last decade have shown that Kv7 channels play a key role in various smooth muscle systems of the body. This review discusses the potential of targeting Kv7 channels in the smooth muscle to treat diseases such as hypertension, bladder instability, constipation and preterm labour.

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Year: 2013 PMID： 22880633 PMCID： PMC3569999 DOI： 10.1111/j.1476-5381.2012.02133.x

Source DB: PubMed Journal: Br J Pharmacol ISSN： 0007-1188 Impact factor: 8.739

78 in total

1. Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell.

Authors: A A Selyanko; J K Hadley; I C Wood; F C Abogadie; P Delmas; N J Buckley; B London; D A Brown
Journal: J Neurosci Date: 1999-09-15 Impact factor: 6.167

2. Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles.

Authors: Thomas A Jepps; Iain A Greenwood; James D Moffatt; Kenton M Sanders; Susumu Ohya
Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-04-23 Impact factor: 4.052

3. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

Authors: M C Sanguinetti; M E Curran; A Zou; J Shen; P S Spector; D L Atkinson; M T Keating
Journal: Nature Date: 1996-11-07 Impact factor: 49.962

Review 4. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

Authors: Neil Brickel; Paul Gandhi; Kevan VanLandingham; Janet Hammond; Sarah DeRossett
Journal: Epilepsia Date: 2012-03-16 Impact factor: 5.864

5. KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology.

Authors: R Søgaard; T Ljungstrøm; K A Pedersen; S P Olesen; B S Jensen
Journal: Am J Physiol Cell Physiol Date: 2001-04 Impact factor: 4.249

6. Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells.

Authors: Shuk Yin M Yeung; Iain A Greenwood
Journal: Br J Pharmacol Date: 2005-10 Impact factor: 8.739

7. KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.

Authors: T Kharkovets; J P Hardelin; S Safieddine; M Schweizer; A El-Amraoui; C Petit; T J Jentsch
Journal: Proc Natl Acad Sci U S A Date: 2000-04-11 Impact factor: 11.205

8. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired β-adrenoceptor-mediated relaxation of renal arteries in hypertension.

Authors: Preet S Chadha; Friederike Zunke; Hai-Lei Zhu; Alison J Davis; Thomas A Jepps; Søren P Olesen; William C Cole; James D Moffatt; Iain A Greenwood
Journal: Hypertension Date: 2012-02-21 Impact factor: 10.190

9. Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.

Authors: S Y M Yeung; V Pucovský; J D Moffatt; L Saldanha; M Schwake; S Ohya; I A Greenwood
Journal: Br J Pharmacol Date: 2007-05-21 Impact factor: 8.739

10. Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.

Authors: I Morecroft; A Murray; M Nilsen; A M Gurney; M R MacLean
Journal: Br J Pharmacol Date: 2009-06-05 Impact factor: 8.739

19 in total

1. The K_V 7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K⁺ channel currents.

Authors: Nathan R Tykocki; Thomas J Heppner; Thomas Dalsgaard; Adrian D Bonev; Mark T Nelson
Journal: J Physiol Date: 2018-12-26 Impact factor: 5.182

One man's side effect is another man's therapeutic opportunity: targeting Kv7 channels in smooth muscle disorders.

1. Two types of K(+) channel subunit, Erg1 and KCNQ2/3, contribute to the M-like current in a mammalian neuronal cell.

2. Molecular and functional characterization of Kv7 K+ channel in murine gastrointestinal smooth muscles.

3. Coassembly of K(V)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.

Review 4. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

5. KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology.

6. Electrophysiological and functional effects of the KCNQ channel blocker XE991 on murine portal vein smooth muscle cells.

7. KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.

8. Reduced KCNQ4-encoded voltage-dependent potassium channel activity underlies impaired β-adrenoceptor-mediated relaxation of renal arteries in hypertension.

9. Molecular expression and pharmacological identification of a role for K(v)7 channels in murine vascular reactivity.

10. Treatment with the Kv7 potassium channel activator flupirtine is beneficial in two independent mouse models of pulmonary hypertension.

1. The K_V 7 channel activator retigabine suppresses mouse urinary bladder afferent nerve activity without affecting detrusor smooth muscle K⁺ channel currents.

Review 2. Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.

Review 3. Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth.

4. Vasorelaxant effects of novel Kv 7.4 channel enhancers ML213 and NS15370.

5. K_V7 channels in the human detrusor: channel modulator effects and gene and protein expression.

6. Cardiovascular responses to retigabine in conscious rats--under normotensive and hypertensive conditions.

Review 7. New antiepileptic medication linked to blue discoloration of the skin and eyes.

8. Selective activation of vascular K_v 7.4/K_v 7.5 K⁺ channels by fasudil contributes to its vasorelaxant effect.

9. Differential activation of vascular smooth muscle Kv7.4, Kv7.5, and Kv7.4/7.5 channels by ML213 and ICA-069673.

Review 10. The yin and yang of K_V channels in cerebral small vessel pathologies.

Review 4. The urinary safety profile and secondary renal effects of retigabine (ezogabine): a first-in-class antiepileptic drug that targets KCNQ (K(v)7) potassium channels.

Review 2. Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.

Review 3. Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth.

Review 7. New antiepileptic medication linked to blue discoloration of the skin and eyes.

Review 10. The yin and yang of KV channels in cerebral small vessel pathologies.

Review 10. The yin and yang of K_V channels in cerebral small vessel pathologies.