Advances in Ca(2+) modulation of gastrointestinal anion secretion and its dysregulation in digestive disorders (Review)

Intracellular calcium (Ca(2+)) is a critical cell signaling component in gastrointestinal (GI) physiology. Cytosolic calcium ([Ca(2+)](cyt)), as a secondary messenger, controls GI epithelial fluid and ion transport, mucus and neuropeptide secretion, as well as synaptic transmission and motility. The key roles of Ca(2+) signaling in other types of secretory cell (including those in the airways and salivary glands) are well known. However, its action in GI epithelial secretion and the underlying molecular mechanisms have remained to be fully elucidated. The present review focused on the role of [Ca(2+)](cyt) in GI epithelial anion secretion. Ca(2+) signaling regulates the activities of ion channels and transporters involved in GI epithelial ion and fluid transport, including Cl(-) channels, Ca(2+)-activated K(+) channels, cystic fibrosis (CF) transmembrane conductance regulator and anion/HCO(3)(-) exchangers. Previous studies by the current researchers have focused on this field over several years, providing solid evidence that Ca(2+) signaling has an important role in the regulation of GI epithelial anion secretion and uncovering underlying molecular mechanisms. The present review is largely based on previous studies by the current researchers and provides an overview of the currently known molecular mechanisms of GI epithelial anion secretion with an emphasis on Ca(2+)-mediated ion secretion and its dysregulation in GI disorders. In addition, previous studies by the current researchers demonstrated that different regulatory mechanisms are in place for GI epithelial HCO(3)(-) and Cl(-) secretion. An increased understanding of the roles of Ca(2+) signaling and its targets in GI anion secretion may lead to the development of novel strategies to inhibit GI diseases, including the enhancement of fluid secretion in CF and protection of the GI mucosa in ulcer diseases.