Ca2+ signaling and fluid secretion by secretory cells of the airway epithelium

Cytoplasmic Ca2+ 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 Ca2+ 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 Ca2+. Many neurotransmitters that regulate secretion from serous acinar cells utilize Ca2+ as a second messenger. Changes in intracellular Ca2+ concentration regulate the activities of ion transporters and channels involved in transepithelial ion transport and fluid secretion, including Ca2+-activated K+ channels and Cl− channels. We also review evidence of interactions of Ca2+ 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 Ca2+ 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.