Membrane potential and bicarbonate secretion in isolated interlobular ducts from guinea-pig pancreas
Membrane potential and bicarbonate secretion in isolated interlobular ducts from guinea-pig pancreas
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DOI：
10.1085/jgp.20028631
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发表时间：
2002-11-01
影响因子：
3.8
通讯作者：
Naruse, S
中科院分区：
文献类型：
--
作者：
Ishiguro, H;Steward, MC;Naruse, S
豚鼠胰腺的小叶间导管细胞以6倍的浓度梯度将HCO3-穿过其管腔膜分泌到富含HCO3(125 Mm)的管腔液中。由于在这些条件下，HCO3-不能通过流明的Cl3-/HCO3-交换来实现，所以我们研究了它是由阴离子电导介导的可能性。为了确定跨越管腔膜的电化学电位梯度是否有利于HCO3外流，我们测量了不同生理条件下微灌流小叶间导管节段的细胞内电位(V-m)。当腔内灌流124 mM的氯离子-25 mM的HCO3-溶液时，静息电位约为-60 mV。用DBcAMP或促胰液素刺激时，由于激活了基底膜上的电生Na+-HCO3-共转运，引起短暂的超极化(类似于5 mV)。随后，由于阴离子流过管腔膜，去极化达到约-50 mV的稳态值。将管腔内HCO3-浓度提高到125 mM，在刺激和未刺激的导管上都会引起超极化(类似于10 mV)。这些结果可以用一个模型来解释，在该模型中，跨腔膜的氯离子外流的去极化效应被细胞内氯离子的耗尽所抵消，而被基侧膜上的Na+-HCO3-共转运的超极化效应所抵消。净效应是在最大刺激期间维持的HCO3-的发光定向电化学势梯度。我们的计算表明，在这种梯度的驱动下，HCO3-通过CFTR向管腔的电扩散流出将足以完全解释观察到的HCO3-的分泌通量。
The interlobular duct cells of the guinea-pig pancreas secrete HCO3- across their luminal membrane into a HCO3--rich (125 mM) luminal fluid against a sixfold concentration gradient. Since HCO3- transport cannot be achieved by luminal Cl-/HCO3- exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. To determine whether the electrochemical potential gradient across the luminal membrane would favor HCO3- efflux, we have measured the intracellular potential (V-m) in microperfused, interlobular duct segments under various physiological conditions. When the lumen was perfused with a 124 mM Cl--25 mM HCO3- solution, a condition similar to the basal state, the resting potential was approximately -60 mV Stimulation with dbcAMP or secretin caused a transient hyperpolarization (similar to5 mV) due to activation of electrogenic Na+-HCO3- cotransport at the basolateral membrane. This was followed by depolarization to a steady-state value of approximately -50 mV as a result of anion efflux across the luminal membrane. Raising the luminal HCO3- concentration to 125 mM caused a hyperpolarization (similar to10 mV) in both stimulated and unstimulated ducts. These results can be explained by a model in which the depolarizing effect of Cl- efflux across the luminal membrane is minimized by the depletion of intracellular Cl- and offset by the hyperpolarizing effects of Na+-HCO3- cotransport at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO3- that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO3- to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO3-.