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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. Mechanisms altering airway smooth muscle cell Ca(2+) homeostasis in two asthma models
Background: Asthma is characterized by airway remodeling, altered
mucus production and airway smooth muscle cell (ASMC) contraction
causing extensive airway narrowing. In particular, alterations of
ASMC contractility seem to be of crucial importance. The elevation
of the cytoplasmic Ca(2+) concentration is a key event leading to
ASMC contraction and changes in the agonist- induced Ca(2+)
increase in ASMC have been reported in asthma. Objective: The aim
of this study was to investigate mechanisms underlying these
changes. Methods: Murine tracheal smooth muscle cells (MTSMC) from
T- bet KO mice and human bronchial smooth muscle cells (HBSMC)
incubated with IL-13 and IL-4 served as asthma models.
Acetylcholine- induced changes in the cytoplasmic Ca(2+)
concentration were recorded using fluorescence microscopy and the
expression of Ca(2+) homeostasis regulating proteins was
investigated with Western blot analysis. Results: Acetylcholine-
induced Ca(2+) transients were elevated in both asthma models. This
correlated with an increased Ca(2+) content of the sarcoplasmic
reticulum (SR). In MTSMC from T-bet KO mice, the expression of the
SR Ca(2+) buffers calreticulin and calsequestrin was higher
compared to wild- type mice. In HBSMC incubated with IL-13 or IL-4,
the expression of ryanodine receptors, inositol-3-phosphate
receptors and sarcoplasmic/ endoplasmic reticulum Ca 2+ ATPases 2
was increased compared to HBSMC without incubation with
interleukins. The enlarged acetylcholine- induced Ca(2+) transients
could be reversed by blocking inositol-3- phosphate receptors.
Conclusions: We conclude that in the murine asthma model the SR
Ca(2+) buffer capacity is increased, while in the human asthma
model the expression of SR Ca(2+) channels is altered. The
investigation of the Ca(2+) homeostasis of ASMC has the potential
to provide new therapeutical options in asthma. Copyright (C) 2008
S. Karger AG, Basel.

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