Figure 1.

Ion channels in exocrine pancreas. Illustration of the structure of acinar and major ductal segments of secretory glands in pancreas. Acinar cells secrete digestive enzymes (orange circles in acini) and an isotonic NaCl rich fluid which transports the enzymes to the ducts. Fluid secretion in acini cells is regulated by a Cl^- secretion process. Cl^- secretion is activated by [Ca²⁺]_i, from a Ca²⁺ influx through SOCs in the basolateral membrane, where Cl^- channels, Ca²⁺ activated Cl^- channels (CaCC) and different types of K⁺ channels are activated to provide the efflux of their respected ions. K⁺ channels also create a driving force by maintaining a negative membrane potential. The negative charge mediated by a high concentration of Cl^- ions results in transport of Na⁺ through tight junctions to the luminal space. NaCl makes the driving force for water to efflux through aquaporins and a cell shrinkage. This cell shrinkage reduces [Ca²⁺]_i, which inhibits Cl^- and K⁺ efflux through their channels and in parallel activates basolateral transporters and pumps to restore both Cl^- and K⁺. The digestive enzymes are transported in the NaCl isotonic fluid to the ducts, which is low in HCO₃^- concentration in the proximal ducts, but this concentration increases through the transport to the distal duct cells. The ductal fluid becomes rich in HCO₃^-, by a two-step process. The first step takes place in the proximal ducts, where Cl^-/HCO₃^- exchangers secretes HCO₃^- and absorb Cl^- and Cl^- channels recycle Cl^-. As in the acinar cells an osmotic reaction happens, where efflux of negative HCO₃^- and Na⁺ drives water flow through aquaporins. This results in high concentration of HCO₃^- (~100 mM), a low concentration of Cl^- (~25 mM) and a high fraction of water in the pancreatic juice. The second step takes place in the distal part of the ducts, where the specific Cl^- channel CFTR changes selectivity to HCO₃^- and function as a HCO₃^- efflux channel to determine the final concentration of the HCO₃^- rich fluid (~140 mM). K⁺ channels may, as in acini, take part in the secretion of K⁺ and regulation of anion transport by maintaining the membrane potential in both the basolateral and luminal membrane. SOCs ensure the influx of Ca²⁺ which takes part in regulation of ion channels through [Ca²⁺]_i as in acini. Activation or inhibition of P2 receptors by Ca²⁺ signaling also regulate anion secretion through K⁺ and Cl^- channels.