HCO3− Transport in a Mathematical Model of the Pancreatic Ductal Epithelium

HCO3− Transport in a Mathematical Model of the Pancreatic Ductal Epithelium
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胰腺导管上皮数学模型中的 HCO3− 运输

DOI:
10.1007/s00232001077
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发表时间:
2000
期刊:
The Journal of Membrane Biology
影响因子:
--
通讯作者:
B. Argent
B. Argent
中科院分区:
--
文献类型:
--
作者:
Y. Sohma;M. Gray;Y. Imai;B. Argent

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抽象的。我们已经使用计算机建模来研究胰管细胞如何分泌含有近等渗(约140 mm)NaHCO 3的液体。实验数据表明,NaHCO 3的分泌分三步进行:(i)通过Na(HCO 3)n共转运蛋白、Na+/H+交换蛋白和质子泵使HCO −3累积穿过导管细胞的基底外侧膜;(ii)通过Cl−/HCO−3反向转运蛋白分泌穿过管腔膜,该反向转运蛋白与Cl−通道平行工作;(iii)Na+通过细胞旁途径扩散。将目前可用的实验数据编入我们的计算机模型表明,这种HCO−3分泌机制在一个重要方面存在缺陷。虽然它可以产生相对较大体积的富含HCO−3的液体,但它只能将管腔HCO−3浓度提高到约70 mm。为了通过模型实现140 mm NaHCO 3的分泌,必须:(i)降低导管细胞腔膜的传导性Cl−渗透性并增加传导性HCO−3渗透性,和(ii)降低管腔Cl−/HCO−3反向转运蛋白的活性。在这些条件下,大多数HCO−3通过传导途径分泌。根据我们的数据,我们提出HCO−3的分泌主要是通过腺泡附近导管段的反向转运蛋白(管腔HCO−3浓度高达1070 mm)进行的,但主要是通过导管树下游的通道(将管腔HCO−3升高至10140 mm)。
Abstract. We have used computer modeling to investigate how pancreatic duct cells can secrete a fluid containing near isotonic (∼140 mm) NaHCO3. Experimental data suggest that NaHCO3 secretion occurs in three steps: (i) accumulation of HCO−3 across the basolateral membrane of the duct cell by Na(HCO3)n cotransporters, Na+/H+ exchangers and proton pumps; (ii) secretion of HCO−3 across the luminal membrane on Cl−/HCO−3 antiporters operating in parallel with Cl− channels; and (iii) diffusion of Na+ through the paracellular pathway. Programming the currently available experimental data into our computer model shows that this mechanism for HCO−3 secretion is deficient in one important respect. While it can produce a relatively large volume of a HCO−3-rich fluid, it can only raise the luminal HCO−3 concentration up to about 70 mm. To achieve secretion of 140 mm NaHCO3 by the model it is necessary to: (i) reduce the conductive Cl− permeability and increase the conductive HCO−3 permeability of the luminal membrane of the duct cell, and (ii) reduce the activity of the luminal Cl−/HCO−3 antiporters. Under these conditions most of the HCO−3 is secreted via a conductive pathway. Based on our data, we propose that HCO−3 secretion occurs mainly by the antiporter in duct segments near the acini (luminal HCO−3 concentration up to ∼70 mm), but mainly via channels further down the ductal tree (raising luminal HCO−3 to ∼140 mm).
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发表时间: 1988
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