Calcium signaling in pancreatic ductal epithelial cells: An old friend and a nasty enemy

Ductal epithelial cells of the exocrine pancreas secrete HCO3− rich, alkaline pancreatic juice, which maintains the intraluminal pH and washes the digestive enzymes out from the ductal system. Importantly, damage of this secretory process can lead to pancreatic diseases such as acute and chronic pancreatitis. Intracellular Ca2+ signaling plays a central role in the physiological regulation of HCO3− secretion, however uncontrolled Ca2+ release can lead to intracellular Ca2+ overload and toxicity, including mitochondrial damage and impaired ATP production. Recent findings suggest that the most common pathogenic factors leading to acute pancreatitis, such as bile acids, or ethanol and ethanol metabolites can evoke different types of intracellular Ca2+ signals, which can stimulate or inhibit ductal HCO3− secretion. Therefore, understanding the intracellular Ca2+ pathways and the mechanisms which can switch a good signal to a bad signal in pancreatic ductal epithelial cells are crucially important. This review summarizes the variety of Ca2+ signals both in physiological and pathophysiological aspects and highlight molecular targets which may strengthen our old friend or release our nasty enemy.