Stimulus-response coupling in mammalian ciliated cells. Demonstration of two mechanisms of control for cytosolic [Ca2+]

Abstract

Changes of cytosolic [Ca2+] have been proposed to couple stimulation of ciliary movement, however, quantitative measurements of fluctuations of intracellular free [Ca2+] associated with stimulation of ciliated cells have not been investigated. In primary cultures of rabbit oviductal ciliated cells, the stimulation of ciliary activity produced by micromolar concentrations of adenosine triphosphate (ATP) and prostaglandin F2 alpha (PGF2 alpha) was associated with a transient increase of intracellular [Ca2+]. Whereas the increase of cytosolic [Ca2+] and beat frequency produced by ATP were inhibited by the Ca-channel blocker LaCl3, the rise of cytosolic [Ca2+] and frequency of ciliary beat produced by PGF2 alpha was not affected by LaCl3. These results are the first direct demonstration that fluctuations of cytosolic [Ca2+] are associated with increased ciliary beat frequency in mammalian epithelial cells. The present findings suggest two different calcium-dependent mechanisms for stimulus-coupling in ciliary epithelium: ATP acting via purinergic receptor coupled to transmembrane influx of Ca2+, and PGF2 alpha acting via receptor-mediated release of intracellular sequestered Ca.

Inhalation of dry-powder mannitol increases mucociliary clearance

“…Shrinking of the epithelial cells is followed by a regulatory volume increase (RVI) which initiates biochemical events leading to an increase in intracellular calcium [Ca 2+ ] i [12]. An increase in [Ca 2+ ] i has been shown to increase ciliary activity [13][14][15]. Hyperosmolarity also causes depolarization of the epithelial cell membrane [16] which could cause an increase in ciliary beat frequency, as the work by MAO and WONG [17] suggests, dependent on the influx of sodium or Ca 2+ .…”

Nervous control of ciliary beating by Cl-, Ca2+ and calmodulin inTritonia diomedea

“…Ca 2+ release from stores contributes to excitation of CBF Increases in [Ca 2+ ] in are well established as a prerequisite for CBF excitation (Verdugo, 1980;Villalon et al, 1989;Salathe and Bookman, 1995;Korngreen and Priel, 1996), but the source of the Ca 2+ , e.g. from stores or influx, remains unclear.…”

“…A key step in increasing CBF in multicellular organisms or reversing directions, in e.g. paramecium (Eckert, 1972), is an increase in internal free Ca 2+ (Verdugo, 1980;Villalon et al, 1989;Salathe and Bookman, 1995;Korngreen and Priel, 1996). Studies of CBF have yielded different possible mechanisms for increasing internal free Ca 2+ , including the phospholipase C (PLC) pathway (Christopher et al, 1999;Zagoory et al, 2001), both protein kinase C (PKC) (Gertsberg et al, 1997;Christopher et al, 1999;Barrera et al, 2004) and protein kinase A (PKA) (Braiman et al, 1998;Zagoory et al, 2002;Lieb et al, 2002), inositol 1,4,5-triphosphate (Barrera et al, 2004), nitrous oxide (Uzlander and Priel, 1999;Runer and Lindberg, 1999;Doran et al, 2003) and cAMP (Stommel and Stephens, 1985;Aiello, 1990).…”

The lactoperoxidase system links anion transport to host defense in cystic fibrosis

“…Normal human airway epithelia also actively produce H 2 O 2 at the apical surface using Duox and release it into the apical surface liquid [18]. This airway H 2 O 2 production is increased through stimulation of purinergic receptors [18] that also act to increase mucus secretion [19,20] and ciliary beating [21][22][23] LPO system is present in the airway lumen and can be regulated in concert with other facets of the airway host defense. Since the LPO system is effective against staphylococci [24], E. coli and pseudomonads [24][25][26] and since SCN À is a requisite substrate for LPO, defects in SCN À transport and resulting loss of LPO activity could contribute, at least partially, to the chronic respiratory infections seen in CF patients.…”