Calcium-activated chloride conductance in a pancreatic adenocarcinoma cell line of ductal origin (HPAF) and in freshly isolated human pancreatic duct cells

1998 ◽  
Vol 435 (6) ◽  
pp. 796-803 ◽  
Author(s):  
J. P. Winpenny ◽  
A. Harris ◽  
M. A. Hollingsworth ◽  
B. E. Argent ◽  
M. A. Gray
2003 ◽  
Vol 285 (2) ◽  
pp. C433-C445 ◽  
Author(s):  
Peying Fong ◽  
Barry E. Argent ◽  
William B. Guggino ◽  
Michael A. Gray

Pancreatic duct cells express a Ca2+-activated Cl- conductance (CaCC), upregulation of which may be beneficial to patients with cystic fibrosis. Here, we report that HPAF, a human pancreatic ductal adenocarcinoma cell line that expresses CaCC, develops into a high-resistance, anion-secreting epithelium. Mucosal ATP (50 μM) caused a fourfold increase in short-circuit current ( I sc), a hyperpolarization of transepithelial potential difference (from -4.9 ± 0.73 to -8.5 ± 0.84 mV), and a fall in resistance to less than one-half of resting values. The effects of ATP were inhibited by mucosal niflumic acid (100 μM), implicating an apical CaCC in the response. RT-PCR indicated expression of hClC-2, hClC-3, and hClC-5, but surprisingly not hCLCA-1 or hCLCA-2. K+ channel activity was necessary to maintain the ATP-stimulated I sc. Using a pharmacological approach, we found evidence for two types of K+ channels in the mucosal and serosal membranes of HPAF cells, one activated by chlorzoxazone (500 μM) and sensitive to clotrimazole (30 μM), as well as one blocked by clofilium (100 μM) but not chromanol 293B (5 μM). RT-PCR indicated expression of the Ca2+-activated K+ channel KCNN4, as well as the acid-sensitive, four transmembrane domain, two pore K+ channel, KCNK5 (hTASK-2). Western blot analysis verified the expression of CLC channels, as well as KCNK5. We conclude that HPAF will be a useful model system for studying channels pertinent to anion secretion in human pancreatic duct cells.


2016 ◽  
Vol 36 (5) ◽  
pp. 2875-2883 ◽  
Author(s):  
Pyo June Pak ◽  
Beob Hwa Kang ◽  
Sung Hyo Park ◽  
Ji Hyun Sung ◽  
Yong Hoon Joo ◽  
...  

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