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.
- The American Society for Pharmacology and Experimental Therapeutics