Expression and motor functional roles of voltage-dependent type 7 K(+) channels in the human taenia coli

Maria Martire, Claudio Coco, Diego Curro', Vincenzo Arena, Gianluca Rizzo, Maurizio Taglialatela

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

7 Citazioni (Scopus)

Abstract

Voltage-dependent type 7 K(+) (KV7 or KCNQ) channels modulate the excitability of neurons and muscle cells. The aims of the present study were to investigate the motor effects of KV7 channel modulators and the expression of KV7 channels in the human taenia coli. The effects of KV7 channel modulators on the muscle tone of human taenia coli strips were investigated under nonadrenergic non-nitrergic conditions by organ bath studies. Gene expression and tissue localisation of channels were studied by real-time PCR and immunohistochemistry, respectively. Under basal conditions, the KV7 channel blocker XE-991 induced concentration-dependent contractions, with mean EC50 and Emax of 18.7 μM and 30.5% respectively of the maximal bethanechol-induced contraction, respectively. The KV7 channel activators retigabine and flupirtine concentration-dependently relaxed the taenia coli, with mean EC50s of 19.2 μM and 29.9 μM, respectively. Retigabine also relaxed bethanechol-precontracted strips, with maximal relaxations of 79.2% of the bethanecol-induced precontraction. The motor effects induced by the KV7 channel modulators were not affected by tetrodotoxin or ω-conotoxin GVIA. XE-991 greatly reduced retigabine- and flupirtine-induced relaxations. Transcripts encoded by all KCNQ genes were detected in the taenia coli, with KCNQ4 showing the highest expression levels. KV7.4 channels were clearly visualised by immunohistochemistry in colonic epithelium, circular muscle layer and taenia coli. KV7 channels appear to contribute to the resting muscle tone of the human taenia coli. In addition, KV7 channel activators significantly relax the taenia coli. Thus, they could be useful therapeutic relaxant agents for colonic motor disorders.
Lingua originaleEnglish
pagine (da-a)12-20
Numero di pagine9
RivistaEuropean Journal of Pharmacology
Volume721
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • K(V)7 channels
  • KCNQ channels
  • Retigabine
  • taenia coli

Fingerprint

Entra nei temi di ricerca di 'Expression and motor functional roles of voltage-dependent type 7 K(+) channels in the human taenia coli'. Insieme formano una fingerprint unica.

Cita questo