Secretory control of basolateral membrane potassium and chloride channels in colonic crypt cells.

Secretory control of basolateral membrane potassium and chloride channels in colonic crypt cells.
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结肠隐窝细胞基底外侧膜钾和氯通道的分泌控制。

DOI:
10.1007/0-387-23752-6_11
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发表时间:
2004
影响因子:
--
通讯作者:
Halm,DanR
Halm,DanR
中科院分区:
医学4区
文献类型:
--
作者:
Halm,DanR

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跨上皮的液体分泌通常是由离子的活跃分泌驱动的,并起到润滑表面和推动黏液等大分子的作用。在结肠上皮中,cl和K+的分泌被激活,以驱动水进入管腔。有几种类型的信号启动这种分泌,包括神经活动和肠道细胞释放的旁分泌。肠粘膜和肌肉细胞释放的胆碱能神经和前列腺素是cl和K+分泌的两种有效刺激物。K+分泌不同时分泌cl也通过这些途径刺激,特别是肾上腺素通过肾上腺素能受体和前列腺素e2通过前列腺素类EP2受体作用。3,4初级K+分泌的细胞机制与cl分泌的标准模型相似,只是顶端膜的cl通道不需要打开(图1)。K+和cl分泌的功能测量5-7支持结肠隐窝柱状细胞能够两种离子分泌模式的概念,并且仅仅通过激活不同的离子转运体来响应不同类型的分泌剂。因此,K+分泌依赖于基底外膜中Na+: K+: 2Cl——共转运体的运作,这需要另一种转运蛋白协调cl -出口穿过基底外膜。同时,基底外侧膜cl通道的存在可以满足维持细胞内cl浓度和膜电位差稳定的要求。激活cl -或K+分泌显然需要增加每一种相关转运蛋白的流量(图1)。对于这些离子分泌物,驱动力的变化太小,不足以引起流量的增加。在结肠上皮持续的离子分泌过程中,离子浓度梯度5,6和膜电位在很大程度上是不变的,因此每种转运体的通透性必须通过在膜上出现更多的数量或通过更高的活性来增加。显然,维持相当稳定的细胞
Fluid secretion across epithelia generally is driven by the active secretion of ions and serves to lubricate surfaces and propel macromolecules such as mucus. 1, 2 In the colonic epithelium, secretion of Cl-and K+ is activated to drive water movement into the lumen. Several types of signals act to initiate this secretion, including nerve activity and paracrine release from cells in the intestine. Two potent stimulators of this Cl-and K+ secretion are cholinergic nerves and prostaglandins released from cells in the intestinal mucosa and muscle. K+ secretion without concurrent Cl-secretion also is stimulated through these routes, specifically by epinephrine acting via-adrenergic receptors and by prostaglandin-E2 acting via prostanoid EP2 receptors. 3, 4 The cellular mechanism for primary K+ secretion3 is similar to the standard model for Cl-secretion, 1 except that apical membrane Cl-channels need not open (Figure 1). Functional measures of K+ and Cl-secretion5-7 support the concept that the columnar cells of colonic crypts are capable of both modes of ion secretion, and simply respond to distinct classes of secretagogues by activating different sets of ion transporters. Thus, the dependence of K+ secretion on operation of Na+: K+: 2Cl--cotransporters in the basolateral membrane requires that another transport protein coordinates Cl-exit back across the basolateral membrane. Together, the requirements for maintaining a stable intracellular Cl-concentration and membrane electrical potential difference could be satisfied by the presence of basolateral membrane Cl-channels. Activation of either Cl-or K+ secretion obviously requires increased flow through each one of the transport proteins involved (Figure 1). For these ion secretions, the changes in driving forces are too small to be responsible for the increased flow. Both the ion concentration gradients5, 6 and membrane electrical potential7 are largely unchanged during sustained ion secretion in the colonic epithelium, so that the permeability of each transporter must increase either through greater numbers becoming present in the membrane or by higher activity. Apparently, maintaining a fairly constant cellular
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