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首页> 外文期刊>American Journal of Physiology >Role of Ca2+-activated K+ channels in duodenal mucosal ion transport and bicarbonate secretion.
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Role of Ca2+-activated K+ channels in duodenal mucosal ion transport and bicarbonate secretion.

机译：Ca2 +激活的K +通道在十二指肠粘膜离子转运和碳酸氢根分泌中的作用。

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Stimulation of muscarinic receptors in the duodenal mucosa raises cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)), thereby regulating duodenal epithelial ion transport. However, little is known about the downstream molecular targets that account for this Ca(2+)-mediated biological action. Ca(2+)-activated K(+) (K(Ca)) channels are candidates, but the expression and function of duodenal K(Ca) channels are poorly understood. Therefore, we determined whether K(Ca) channels are expressed in the duodenal mucosa and investigated their involvement in Ca(2+)-mediated duodenal epithelial ion transport. Two selective blockers of intermediate-conductance Ca(2+)-activated K(+) (IK(Ca)) channels, clotrimazole (30 muM) and 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34; 10 muM), significantly inhibited carbachol (CCh)-induced duodenal short-circuit current (I(sc)) and duodenal mucosal bicarbonate secretion (DMBS) in mice but did not affect responses to forskolin and heat-stable enterotoxin of Escherichia coli. Tetraethylammonium, 4-aminopyridine, and BaCl(2) failed to inhibit CCh-induced I(sc) and DMBS. A-23187 (10 muM), a Ca(2+) ionophore, and 1-ethyl-2-benzimidazolinone (1-EBIO; 1 mM), a selective opener of K(Ca) channels, increased both I(sc) and DMBS. The effect of 1-EBIO was more pronounced with serosal than mucosal addition. Again, both clotrimazole and TRAM-34 significantly reduced A23187- or 1-EBIO-induced I(sc) and DMBS. Moreover, clotrimazole (20 mg/kg ip) significantly attenuated acid-stimulated DMBS of mice in vivo. Finally, the molecular identity of IK(Ca) channels was verified as KCNN4 (SK4) in freshly isolated murine duodenal mucosae by RT-PCR and Western blotting. Together, our results suggest that the IK(Ca) channel is one of the downstream molecular targets for [Ca(2+)](cyt) to mediate duodenal epithelial ion transport.
机译：十二指肠粘膜中毒蕈碱受体的刺激提高了胞浆中游离Ca（2+）的浓度（[Ca（2 +）]（cyt）），从而调节了十二指肠上皮离子的转运。但是，了解到的下游分子目标，这占Ca（2+）介导的生物学作用知之甚少。 Ca（2+）激活K（+）（K（Ca））通道是候选，但对十二指肠K（Ca）通道的表达和功能了解甚少。因此，我们确定K（Ca）通道是否在十二指肠粘膜中表达，并调查其参与Ca（2+）介导的十二指肠上皮离子运输。两个选择性阻滞剂的中等导电性Ca（2+）激活的K（+）（IK（Ca））通道，克霉唑（30μM）和1-[（（2-氯苯基）二苯甲基] -1H-吡唑（TRAM-34 ; 10μM）显着抑制小鼠中的卡巴胆碱（CCh）诱导的十二指肠短路电流（I（sc））和十二指肠粘膜碳酸氢盐分泌（DMBS），但不影响对福司可林和热稳定肠毒素的反应。四乙铵，4-氨基吡啶和BaCl（2）未能抑制CCh诱导的I（sc）和DMBS。 A-23187（10μM），Ca（2+）离子载体和1-乙基-2-苯并咪唑啉酮（1-EBIO; 1 mM），K（Ca）通道的选择性开放剂增加了I（sc）和DMBS。浆膜比黏膜添加对1-EBIO的影响更为明显。同样，克霉唑和TRAM-34均显着降低A23187-或1-EBIO诱导的I（sc）和DMBS。此外，克霉唑（20 mg / kg ip ip）在体内显着减轻了酸刺激小鼠的DMBS。最后，通过RT-PCR和Western印迹在新鲜分离的鼠十二指肠粘膜中将IK（Ca）通道的分子身份验证为KCNN4（SK4）。在一起，我们的结果表明，IK（Ca）通道是[Ca（2 +）]（cyt）介导十二指肠上皮离子运输的下游分子靶标之一。

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