RT Journal Article
SR Electronic
T1 Enhancement of Ca<sup>2+</sup> influx and ciliary beating by membrane hyperpolarization due to ATP-sensitive K<sup>+</sup> channel opening in mouse airway epithelial cells
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.113.205138
DO 10.1124/jpet.113.205138
A1 Ohba, Teruya
A1 Sawada, Eiji
A1 Suzuki, Yoshiaki
A1 Yamamura, Hisao
A1 Ohya, Susumu
A1 Tsuda, Hiroyuki
A1 Imaizumi, Yuji
YR 2013
UL http://jpet.aspetjournals.org/content/early/2013/08/06/jpet.113.205138.abstract
AB Among the several types of cells composing the airway epithelium, the ciliated 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 Ca2+ concentration ([Ca2+]i) are the main driving force controlling the ciliary activity. In mouse ciliated cells, membrane hyperpolarization from -20 to -60 mV under whole cell voltage-clamp induced a slow but significant [Ca2+]i rise in a reversible manner. This rise was completely inhibited by the removal of Ca2+ 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 addition of 10 μM diazoxide and suppressed by subsequent addition of 5 μM glibenclamide. In addition, the application of 10 μM diazoxide induced a significant [Ca2+]i rise and facilitated ciliary movement. Multi-cell RT-PCR analyses suggested that Kir6.2 and SUR2B transcripts are expressed in ciliated cells. The confocal Ca2+ imaging analyses suggested that the [Ca2+]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 [Ca2+]i rise via the facilitation of Ca2+ influx through the non-voltage dependent Ca2+ permeable channels. Therefore, a KATP opener may be beneficial in facilitating ciliary movement.