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首页> 外文期刊>Gut: Journal of the British Society of Gastroenterology >Evidence that two distinct crypt cell types secrete chloride and potassium in human colon
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Evidence that two distinct crypt cell types secrete chloride and potassium in human colon

机译：两种不同的隐窝细胞类型在人结肠中分泌氯和钾的证据

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Background Human colon may secrete substantial amounts of water secondary to chloride (Cl-) and/or potassium (K+) secretion in a variety of diarrhoeal diseases. Ion secretion occurs via Cl- and K+ channels, which are generally assumed to be co-located in the colonocyte apical membrane, although their exact cellular sites remain unclear. Objective To investigate the location of apical Cl- (CFTR) and apical K+ (large conductance; BK) channels within human colonic epithelium. Design Whole-cell patch clamp recordings were obtained from intact human colonic crypts. Specific blockers of K+ channels and CFTR identified different types of K+ channel and CFTR under resting conditions and after stimulating intracellular cAMP with forskolin. The BK channel β3-subunit was localised by immunostaining. Results Two types of crypt cells were identified. One (73% of cells) had whole-cell currents dominated by intermediate conductance (IK) K+ channels under resting conditions, which developed large CFTR-mediated currents in response to increasing intracellular cAMP. The other (27% of cells) had resting currents dominated by BK channels inhibited by the BK channel blocker penitrem A, but insensitive to both forskolin and the IK channel blocker clotrimazole. Immunostaining showed co-localisation of the BK channel β3-subunit and the goblet cell marker, MUC2. Conclusions In human colon, Cl- secretion originates from the dominant population of colonocytes expressing apical CFTR, whereas K+ secretion is derived from a smaller population of goblet cells expressing apical BK channels. These findings provide new insights into the pathophysiology of secretory diarrhoea and should be taken into account during the development of antidiarrhoeal drugs.
机译：背景技术在各种腹泻疾病中，人类结肠可能会分泌大量继氯化物（Cl-）和/或钾（K +）分泌的水。离子的分泌是通过Cl-和K +通道发生的，尽管它们的确切细胞位置仍不清楚，但通常假定它们共同位于结肠细胞顶膜中。目的探讨人结肠上皮细胞内Cl-（CFTR）和K +（大电导; BK）通道的位置。设计从完整的人类结肠隐窝获得全细胞膜片钳记录。在静息条件下以及用毛喉素刺激细胞内cAMP后，K +通道和CFTR的特定阻滞剂鉴定出不同类型的K +通道和CFTR。 BK通道β3-亚基通过免疫染色定位。结果鉴定出两种类型的隐窝细胞。其中一个（占细胞的73％）在静息条件下具有由中间电导（IK）K +通道控制的全细胞电流，该细胞响应于细胞内cAMP的增加而产生大CFTR介导的电流。另一个（27％的细胞）具有由BK通道阻滞剂Penitrem A抑制的BK通道主导的静止电流，但对毛喉素和IK通道阻滞剂克霉唑均不敏感。免疫染色显示BK通道β3-亚基和杯状细胞标记物MUC2共同定位。结论在人类结肠中，Cl-分泌起源于表达顶端CFTR的主要结肠细胞群，而K +分泌起源​​于少数表达顶端BK通道的杯状细胞。这些发现为分泌性腹泻的病理生理学提供了新的见识，在开发止泻药时应予以考虑。

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