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Purinergic regulation of ion transport in Capan‐1 cell monolayers
Author(s) -
Wang Jing,
Novak Ivana
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1113.2
Subject(s) - purinergic receptor , channel blocker , chemistry , ouabain , ion transporter , secretion , niflumic acid , chloride channel , stimulation , transepithelial potential difference , membrane potential , potassium channel , ussing chamber , epithelial sodium channel , endocrinology , medicine , reversal potential , apical membrane , biophysics , patch clamp , biochemistry , biology , sodium , extracellular , receptor , membrane , organic chemistry , calcium
The aim of the present study was to develop a human pancreatic duct model and elucidate the purinergic signaling regulation of ion transport in pancreatic ducts. Human pancreatic duct cells, capan‐1 were grown on permeable supports. Transepithelial potential (Vte) was measured in open‐circuit Ussing chamber in physiological buffers. Capan‐1 cells formed monolayers with resting transepithelial resistance 404±25 Ω·cm 2 (n=35). Serosal ATP (100 μM) transiently increased Vte from −1.4±0.2 to −4.7±0.4 mV and short‐circuit current (Isc) by 14± 0.8 μA/cm 2 , while mucosal ATP increased Vte by −3.6±0.3 mV and Isc by 13±1 μA/cm 2 (n=28). The Ca 2+ ‐activated Cl − channel (CaCC) blocker niflumic acid (NA, mucosa, 100 μM, n=5) inhibited 44% of mucosal but not serosal ATP effect. The CFTR Cl − channel blocker CFTRinh172 blocked both mucosal and serosal ATP effects (mucosa,10 μM, n=5). The intermediate conductance K + (IK) channel opener DCEBIO (mucosa, 100 μM, n=5) increased mucosal ATP effect, and DCEBIO stimulation was completely inhibited by NA and CFTRinh172 (n=8). The IK channel blocker, clotrimazole, abolished mucosal and serosal ATP effects (30 μM, n=6). In conclusion, mucosal ATP opens both CFTR and CaCC and may stimulate pancrea secretion, while serosal ATP regulates secretion partly through CFTR. In addition, ATP stimulation also regulates IK channels that provide the driving force for Cl − channel dependent secretions.