当前位置： SCI文献检索 > GUT期刊下所有文献 > Pathophysiological relevance of apical large-conductance Ca²+-activated potassium channels in pancreatic duct epithelial cells.

Pathophysiological relevance of apical large-conductance Ca²+-activated potassium channels in pancreatic duct epithelial cells.

Abstract：

BACKGROUND:Acute pancreatitis is among the few inflammatory diseases for which no specific pharmacological treatment is available. It has previously been shown that bile acids alter pancreatic ductal secretion and these effects are probably involved in the pathogenesis of bile-induced pancreatitis. OBJECTIVE:To understand the mechanism responsible for bile-induced hypersecretion and, in particular, to identify the molecular target for bile acids in native pancreatic duct epithelial cells (PDECs). METHODS:Patch clamp recordings and spectrofluorimetry were used to measure whole cell currents and rates of HCO₃⁻ secretion, respectively, from isolated guinea pig pancreatic ducts. Expression of ion channels and receptors was investigated by immunohistochemistry/immunofluorescence of intact pancreatic tissue. RESULTS:Exposing PDECs to chenodeoxycholate (CDC, 100 μM) reversibly increased whole cell K(+) currents and hyperpolarised cell membrane potential. Bile acid-stimulated K(+) currents were inhibited by Ba²(+) (2 mM), iberiotoxin (100 nM), and suppressed by strong intracellular Ca²(+) buffering. Luminally applied iberiotoxin also blocked CDC-stimulated HCO₃⁻secretion from microperfused ducts; however, the inhibitor did not influence the stimulatory effect of secretin, carbachol or luminally applied ATP. The specific large-conductance Ca²(+)-activated potassium (BK) channel activator, NS11021, induced a similar increase in HCO₃⁻secretion to CDC. Immunohistochemical analysis showed strong BK channel protein expression on the apical membrane of PDECs, while the G-protein-coupled bile acid receptor-1 was not detected in PDECs, but was present in acinar cells. CONCLUSION:It was shown for the first time that BK channels (i) are expressed at the apical membrane of guinea pig PDECs; (ii) have a crucial role in regulating HCO₃⁻ secretion and (iii) are also essential for the bile acid-induced hypersecretion and, therefore, underlie the response of the pancreas to this noxious agent.

journal_name

Gut

journal_title

Gut

authors

Venglovecz V,Hegyi P,Rakonczay Z Jr,Tiszlavicz L,Nardi A,Grunnet M,Gray MA

doi

10.1136/gut.2010.214213

subject

Has Abstract

pub_date

2011-03-01 00:00:00

pages

361-9

issue

eissn

0017-5749

issn

1468-3288

pii

gut.2010.214213

journal_volume

pub_type

杂志文章

在线工具

Pathophysiological relevance of apical large-conductance Ca²+-activated potassium channels in pancreatic duct epithelial cells.