Ca²⁺ signaling and fluid secretion by secretory cells of the airway epithelium.
Cytoplasmic Ca(2+) is a master regulator of airway physiology; it controls fluid, mucus, and antimicrobial peptide secretion, ciliary beating, and smooth muscle contraction. The focus of this review is on the role of cytoplasmic Ca(2+) in fluid secretion by airway exocrine secretory cells. Airway submucosal gland serous acinar cells are the primary fluid secreting cell type of the cartilaginous conducting airways, and this review summarizes the current state of knowledge of the molecular mechanisms of serous cell ion transport, with an emphasis on their regulation by intracellular Ca(2+). Many neurotransmitters that regulate secretion from serous acinar cells utilize Ca(2+) as a second messenger. Changes in intracellular Ca(2+) concentration regulate the activities of ion transporters and channels involved in transepithelial ion transport and fluid secretion, including Ca(2+)-activated K(+) channels and Cl(-) channels. We also review evidence of interactions of Ca(2+) signaling with other signaling pathways (cAMP, NO) that impinge upon different ion transport pathways, including the cAMP/PKA-activated cystic fibrosis (CF) transmembrane conductance regulator (CFTR) anion channel. A better understanding of Ca(2+) signaling and its targets in airway fluid secretion may identify novel strategies to intervene in airway diseases, for example to enhance fluid secretion in CF airways.
Department of Otorhinolaryngology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States.
Robert J
RJ
Lee
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States. Electronic address: foskett@mail.med.upenn.edu.
J Kevin
JK
Foskett
D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005088:Exocrine Glands / Q000166:cytology / Q000378:metabolism; D007113:Immunity, Innate; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology*
D053496:Inositol 1,4,5-Trisphosphate Receptors; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP
Airway surface liquid; Bicarbonate; CFTR; Calcium; Cell imaging; Chloride; Cystic fibrosis; Electrophysiology; Epithelial transport; Exocrine; Innate immunity; Inositol trisphosphate receptor; Lung; Mucociliary clearance; Submucosal gland; TMEM16A; cAMP