CFTR functions as a bicarbonate channel in pancreatic duct cells.
CFTR functions as a bicarbonate channel in pancreatic duct cells.
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DOI：
10.1085/jgp.200810122
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发表时间：
2009-03
期刊：
影响因子：
--
通讯作者：
Yamamoto A
中科院分区：
文献类型：
--
作者：
Ishiguro H;Steward MC;Naruse S;Ko SB;Goto H;Case RM;Kondo T;Yamamoto A
胰管上皮细胞分泌富含HCO3−的液体的机制依赖于顶膜上的囊性纤维化跨膜电导调节因子。然而，cftr的确切作用仍不清楚。一种可能性是CFTR的HCO3−通透性为顶端HCO3−在最大分泌期间的外流提供了一条途径。因此，我们试图测量由从豚鼠胰腺分离的小叶间导管顶膜上的膜电位变化引起的HCO3-−的电扩散通量。这是通过记录当通过操纵浴液K+浓度改变膜电位时，在发光灌流的导管中发生的细胞内pH(Phi)的变化来完成的。环磷酸腺苷激活的−通量不受氯离子和钠离子的影响，并被−阻断剂CFTRinh-172显著抑制。此外，在从野生型小鼠分离的导管中观察到的类似的HCO3−通量在囊性纤维化(ΔF)小鼠的导管中缺失。在生理条件下，用含有125mMHCO3−和24mMClCO2的溶液对豚鼠导管进行光灌流，以测定生理条件下根尖膜的HCO3−通透性。根据pH值、膜电位和缓冲容量的变化，确定HCO3-−穿过根尖膜的通量和电化学梯度，并用于计算HCO3-−的通透性。在这些条件下，我们对豚鼠导管细胞顶端HCO3−通透性的∼0.1um秒−1的估计接近于解释观察到的HCO3−分泌速率所需的值。这表明cftr在胰管细胞中起着HCO3−通道的作用，并为HCO3−跨顶膜转运提供了重要途径。
Pancreatic duct epithelium secretes a HCO3−-rich fluid by a mechanism dependent on cystic fibrosis transmembrane conductance regulator (CFTR) in the apical membrane. However, the exact role of CFTR remains unclear. One possibility is that the HCO3− permeability of CFTR provides a pathway for apical HCO3− efflux during maximal secretion. We have therefore attempted to measure electrodiffusive fluxes of HCO3− induced by changes in membrane potential across the apical membrane of interlobular ducts isolated from the guinea pig pancreas. This was done by recording the changes in intracellular pH (pHi) that occurred in luminally perfused ducts when membrane potential was altered by manipulation of bath K+ concentration. Apical HCO3− fluxes activated by cyclic AMP were independent of Cl− and luminal Na+, and substantially inhibited by the CFTR blocker, CFTRinh-172. Furthermore, comparable HCO3− fluxes observed in ducts isolated from wild-type mice were absent in ducts from cystic fibrosis (ΔF) mice. To estimate the HCO3− permeability of the apical membrane under physiological conditions, guinea pig ducts were luminally perfused with a solution containing 125 mM HCO3− and 24 mM Cl− in the presence of 5% CO2. From the changes in pHi, membrane potential, and buffering capacity, the flux and electrochemical gradient of HCO3− across the apical membrane were determined and used to calculate the HCO3− permeability. Our estimate of ∼0.1 µm sec−1 for the apical HCO3− permeability of guinea pig duct cells under these conditions is close to the value required to account for observed rates of HCO3− secretion. This suggests that CFTR functions as a HCO3− channel in pancreatic duct cells, and that it provides a significant pathway for HCO3− transport across the apical membrane.
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影响因子：
4.4
作者：
Lohi, H;Kujala, M;Kere, J
通讯作者：
Kere, J
影响因子：
5.5
作者：
Ishiguro, H;Steward, MC;Case, RM
通讯作者：
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DOI：
10.1152/ajpgi.00286.2006
发表时间：
2007-01-01
影响因子：
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作者：
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影响因子：
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作者：
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