Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 776

12.6.2.3 Ciliary Beat Speed

The nasal mucus is displaced toward the pharynx at a speed of 1 to 3 cm/mn.
Because the density of ciliated cells in the tracheobronchial tree decreases distally
(from a proportion of about 22% in the trachea to 3% in generation 3), mucus speed
ranges from 4.9 mm/mn in the trachea to 1.7 mm/mn in generation 3.

12.6.2.4 Ciliary Beat Regulators

Ciliary beat is regulated by intracellular second messengers, such as cAMP and
cGMP as well as Ca 2 + and H + ions [ 1576 ]. Messenger cAMP activates protein
kinase-A localized to the axoneme. Phosphorylation of PKA substrates increase
ciliary beat frequency. Messenger cGMP also raises ciliary beat frequency using
protein kinase-G and possibly PKA kinase. On the other hand, protein kinase-C
lowers ciliary beating. Intracellular pH may affect ciliary beat frequency via dynein
arms.
Increase in intracellular concentration of calcium ions that heightens the ciliary
beat frequency results from Ca 2 + influx from both the extracellular medium
and intracellular stores. Reversal of beat direction is triggered by quick cal-
cium influx through voltage-sensitive calcium channels distributed over the cilium
length [ 1577 ].
Deformations of the cell surface induce a rapid, transient increase in ciliary beat
frequency. Mechanical stimuli of ciliated or non-ciliated cells of the respiratory
epithelium immediately increase the Ca 2 + level via stretch-activated calcium
channels [ 1515 ]. Mechanotransduction in cultured ciliated cells of the respiratory
epithelium is lost when extracellular Ca 2 + is removed.
In addition, mechanical stimuli that excite some respiratory epithelial cells
activate adjacent cells via messenger transmission through gap junctions [ 1578 ].
Calcium waves primed by intra- and intercellular messenger inositol trisphosphate
in cells of the respiratory epithelium indeed coordinate a cooperative increase in
ciliary beat frequency by releasing calcium ions from stores.
Duration of effective, recovery, and rest phases of the ciliary beat cycle depends
on dual regulation of intracellular concentration of cAMP and calcium ions [ 1515 ].
Mucus load yields a local control of the ciliary beat frequency, whereas neurohor-
monal stimuli regulate ciliary activity throughout the respiratory tract.
Ciliary beat frequency rises (duration of the 3 ciliary beat phases decays)
when temperature elevates and intracellular concentrations of cAMP and Ca 2 +
heighten [ 1515 ]. Regulators Ca 2 + and cAMP can regulate ciliary beat frequency
by influencing ATP availability to or its use rate by axonemes. Calcium ions act in
conjunction with calmodulin at some axonemal sites [ 1578 ]. Excitation by cAMP
of ciliary beat frequency follows phosphorylation of axonemal proteins by cAMP-
dependent protein kinase PKA. The latter is a component of ciliary axoneme.
Transient increases in cytosolic Ca 2 + concentration that augment the respiratory
cilium activity in cultures of rabbit oviductal ciliated cells can be caused by