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.