Referenced in: none

Automatically associated channels: Kir6.1 , Kir6.2 , Slo1

Title: Enhancement of Ca(2+) influx and ciliary beating by membrane hyperpolarization due to ATP-sensitive K(+) channel opening in mouse airway epithelial cells.

Authors: Teruya Ohba, Eiji Sawada, Yoshiaki Suzuki, Hisao Yamamura, Susumu Ohya, Hiroyuki Tsuda, Yuji Imaizumi

Journal, date & volume: J. Pharmacol. Exp. Ther., 2013 Oct , 347, 145-53

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23922448

Abstract
Among the several types of cells composing the airway epithelium, the ciliary cells are responsible for one of the most important defense mechanisms of the airway epithelium: the transport of inhaled particles back up into the throat by coordinated ciliary movement. Changes in the cytoplasmic Ca(2+) concentration ([Ca(2+)]i) are the main driving force controlling the ciliary activity. In mouse ciliary cells, membrane hyperpolarization from -20 to -60 mV under whole-cell voltage-clamp induced a slow but significant [Ca(2+)]i rise in a reversible manner. This rise was completely inhibited by the removal of Ca(2+) from the extracellular solution. Application of diazoxide, an ATP-dependent K(+) channel opener, dose-dependently induced a membrane hyperpolarization (EC50 = 2.3 μM), which was prevented by the addition of 5 μM glibenclamide. An inwardly rectifying current was elicited by the application of 10 μM diazoxide and suppressed by subsequent addition of 5 μM glibenclamide. Moreover, the application of 10 μM diazoxide induced a significant [Ca(2+)]i rise and facilitated ciliary movement. Multi-cell reverse-transcription polymerase chain reaction analyses and immunocytochemical staining suggested that the subunit combination of Kir6.2/SUR2B and possibly also Kir6.1/SUR2B is expressed in ciliary cells. The confocal Ca(2+) imaging analyses suggested that the [Ca(2+)]i rise induced by diazoxide occurred preferentially in the apical submembrane region. In conclusion, the application of a KATP channel opener to airway ciliary cells induces membrane hyperpolarization and thereby induces a [Ca(2+)]i rise via the facilitation of Ca(2+) influx through the non-voltage-dependent Ca(2+) permeable channels. Therefore, a KATP opener may be beneficial in facilitating ciliary movement.