Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon
Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon
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DOI：
10.1152/ajpgi.00101.2010
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发表时间：
2010-09-01
影响因子：
4.5
通讯作者：
Rajendran, Vazhaikkurichi M.
中科院分区：
文献类型：
--
作者：
Kumar, N. S. Nanda;Singh, Satish K.;Rajendran, Vazhaikkurichi M.
Nanda Kumar NS，Singh SK，Rajendran VM.通过Kcnn 4通道介导的粘液钾流出为结肠中的产电阴离子分泌提供驱动力。美国生理学杂志胃肠和肝脏生理学299：G707-G714，2010年。首次发表于2010年7月8日; doi：10.1152/ajpgi.00101.2010。中电导K+（Kcnn 4）通道存在于结肠粘膜和浆膜中。然而，只有丝氨酸蛋白酶Kcnn 4通道已被证明是必不可少的激动剂诱导的（cAMP和Ca 2+）阴离子分泌。本研究旨在确定粘膜Kcnn 4通道是否也在结肠阴离子分泌中发挥作用。粘膜-浆膜和浆膜-粘膜单向Rb-86（K+替代品）通量以及短路电流（I-sc;阴离子分泌的测量）在电压钳条件下在远端结肠从大鼠喂养的标准或K+ -免费的饮食。5，6-二氯-1-乙基-1，3-二氢-2H-苯并咪唑-2-酮（DC-EBIO）用于激活Kcnn 4通道。粘液糖DC-EBIO均能诱导正常大鼠远端结肠K+分泌和阴离子分泌。DC-EBIO诱导的K+分泌被非特异性（Ba 2+）和Kcnn 4特异性（TRAM-34）抑制剂完全阻断，但不被大电导K+（伊比利亚毒素），小电导K+（蜂毒肽）或KCNQ 1（色烷醇293 B）特异性阻断剂阻断。Ba 2+和TRAM-34也抑制DC-EBIO增强的阴离子分泌。DC-EBIO增强的阴离子分泌被非特异性阴离子通道阻滞剂5-硝基-2-（3-苯丙氨基）苯甲酸完全抑制，而CFTR [CFTRinh-172，格列本脲]和CaCC（尼氟灭酸）特异性Cl-通道阻滞剂仅部分抑制。与此相反，粘膜DC-EBIO增强的K+和阴离子分泌不存在于远端结肠的饮食K-耗尽大鼠，表明没有粘膜Kcnn 4通道。这些观察结果表明，粘膜Kcnn 4通道能够通过CFTR和CaCC介导驱动激动剂诱导的阴离子分泌，并可能导致伴随腹泻疾病的粪便K+损失。
Nanda Kumar NS, Singh SK, Rajendran VM. Mucosal potassium efflux mediated via Kcnn4 channels provides the driving force for electrogenic anion secretion in colon. Am J Physiol Gastrointest Liver Physiol 299: G707-G714, 2010. First published July 8, 2010; doi: 10.1152/ajpgi.00101.2010.-Intermediate conductance K+ (Kcnn4) channels are present in both mucosal and serosal membranes of colon. However, only serosal Kcnn4 channels have been shown to be essential for agonist-induced (cAMP and Ca2+) anion secretion. The present study sought to determine whether mucosal Kcnn4 channels also play a role in colonic anion secretion. Mucosal-to-serosal and serosal-to-mucosal unidirectional Rb-86 (K+ surrogate) fluxes as well as short-circuit current (I-sc; a measure of anion secretion) were measured under voltage-clamp conditions in distal colon from rats fed either a standard or K+ -free diet. 5,6-Dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DC-EBIO) was used to activate Kcnn4 channels. Mucosal DC-EBIO both induced K+ secretion and enhanced anion secretion in normal rat distal colon. The DC-EBIO-induced K+ secretion was completely blocked by nonspecific (Ba2+) and Kcnn4-specific (TRAM-34) inhibitors, but was not blocked by the large-conductance K+ (iberiotoxin), small-conductance K+ (apamin), or KCNQ1 (chromanol 293B) specific blockers. Ba2+ and TRAM-34 also inhibited DC-EBIO-enhanced anion secretion. The DC-EBIO-enhanced anion secretion was completely inhibited by the nonspecific anion channel blocker 5-nitro-2-(3-phenylpropyl-amino) benzoic acid, whereas it was only partially inhibited by CFTR [CFTRinh-172, glibenclamide]- and CaCC (niflumic acid)-specific Cl- channel blockers. In contrast, mucosal DC-EBIO-enhanced K+ and anion secretion was not present in distal colon of dietary K-depleted rats, indicating absence of mucosal Kcnn4 channels. These observations indicate that mucosal Kcnn4 channels are capable of driving agonist-induced anion secretion mediated via CFTR and CaCC and likely contribute to stool K+ losses that accompany diarrheal illnesses.