Ca-activated K Currents of Pancreatic Duct Cells in Guinea-pig

Ducts play a critical role in whole secretory process as well as acini. First, the ducts provide a frame work for acinar cells, and they also function as a transport pathway for digestive enzyme and fluid secreted from acinar cells. In addition the ducts play a role of ion exchanges and water secretion. For example, in salivary glands, Na, Cl and HCO3 are reabsorbed into the duct cells, while K is secreted into the lumen from the duct cells (Dinudom et al, 1995; Komwatana et al, 1996; Cook et al, 2002). In pancreas, digestive enzymes are secreted from acini and bicarbonate-rich isotonic fluid is supplied from the duct cells. This fluid has several functions. The most important function is the flushing of digestive enzymes secreted by acini toward gut and neutralization of acidic chime which enters the duodenum from the stomach. In cystic fibrosis (CF), one of the fatal hereditary diseases among Caucacians, pancreatic ductal secretions of bicarbonate and fluid are reduced, leading to an increase of the concentration and precipitation of enzymes within duct lumen, followed by duct blockage and destruction of gland (Becq et al, 1993; Winpenny et al, 1995a). Therefore, defects in ductal function may underlie the pathology that occurs in cystic fibrosis, pancreatitis and perhaps hypofunction of salivary glands. During the last decade, there has been many studies on transepithelial Cl transport, including various ionic channels in duct cells; for example, the cystic fibrosis transmembrane conductance regulator (CFTR), Ca activated Cl channel, and volume activated Clchannel (Gray et al, 1990a; Becq et al, 1992; Smith et al, 1995; Verdon et al, 1995; Nguyen et al, 1997; Winpenny et al, 1998). CFTR is a chloride channel regulated by cAMP and acts in parallel with chloride-bicarbonate exchangers to facilitate bicarbonate secretion across the apical plasma membrane of the duct cells (Gray et al, 1993; Winpenny et al, 1995). In CF (cystic fibrosis) cells, reduced bicarbonate secretion results from defective cAMP-activated Cl channels, and these defects are partially compensated with an increased sensitivity of CF cells to purinergic stimulation and alternative activation of Ca-activated Cl channels (Zsembery et al, 2000). Angiotensin II increases intracellular Ca concentration and may elicit activation of Ca-mediated chloride channels (Fink et al, 2002). However, all the Cl transporters in the duct cell membrane can work only when the intracellular electrical Ca-activated K Currents of Pancreatic Duct Cells in Guinea-pig