TY - JOUR
T1 - Airway hydration, apical K+ secretion, and the Large-conductance, Ca2+-activated and voltage-dependent potassium (BK) channel
AU - Kis, Adrian
AU - Krick, Stefanie
AU - Baumlin, Nathalie
AU - Salathe, Matthias
N1 - Funding Information:
Supported by the Cystic Fibrosis Foundation, the Flight Attendant Medical Research Institute, and the National Institutes of Health.
Publisher Copyright:
Copyright © 2016 by the American Thoracic Society.
PY - 2016/4
Y1 - 2016/4
N2 - Large-conductance, calcium-activated, and voltage-gated K+(BK) channels are expressed in many tissues of the human body, where they play important roles in signaling not only in excitable but also in nonexcitable cells. Because BK channel properties are rendered in part by their association with four β and four γ subunits, their channel function can differ drastically, depending on in which cellular system they are expressed. Recent studies verify the importance of apically expressed BK channels for airway surface liquid homeostasis and therefore of their significant role in mucociliary clearance. Here, we review evidence that inflammatory cytokines, which contribute to airway diseases, can lead to reduced BK activity via a functional down-regulation of the 7 regulatory subunit LRRC26. Therefore, manipulation of LRRC26 and pharmacological opening of BK channels represent two novel concepts of targeting epithelial dysfunction in inflammatory airway diseases.
AB - Large-conductance, calcium-activated, and voltage-gated K+(BK) channels are expressed in many tissues of the human body, where they play important roles in signaling not only in excitable but also in nonexcitable cells. Because BK channel properties are rendered in part by their association with four β and four γ subunits, their channel function can differ drastically, depending on in which cellular system they are expressed. Recent studies verify the importance of apically expressed BK channels for airway surface liquid homeostasis and therefore of their significant role in mucociliary clearance. Here, we review evidence that inflammatory cytokines, which contribute to airway diseases, can lead to reduced BK activity via a functional down-regulation of the 7 regulatory subunit LRRC26. Therefore, manipulation of LRRC26 and pharmacological opening of BK channels represent two novel concepts of targeting epithelial dysfunction in inflammatory airway diseases.
KW - Airway surface liquid
KW - BK channels
KW - Mucociliary clearance
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U2 - 10.1513/AnnalsATS.201507-405KV
DO - 10.1513/AnnalsATS.201507-405KV
M3 - Article
C2 - 27115952
AN - SCOPUS:84989231095
VL - 13
SP - S163-S168
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
SN - 2325-6621
ER -