Anionic leak currents through the Na+/monocarboxylate cotransporter SMCT1
Anionic leak currents through the Na+/monocarboxylate cotransporter SMCT1
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DOI：
10.1152/ajpcell.00220.2009
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发表时间：
2010-01-01
影响因子：
5.5
通讯作者：
Lapointe, Jean-Yves
中科院分区：
文献类型：
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作者：
Coady, Michael J.;Wallendorff, Bernadette;Lapointe, Jean-Yves
Coady MJ、Wallendorff B、Bourgeois F、Lapointe J。通过 Na +/- /单羧酸盐协同转运蛋白 SMCT1 的阴离子泄漏电流。 Am J Physiol Cell Physiol 298：C124-C131，2010。首次发表于 2009 年 10 月 28 日； doi:10.1152/ajpcell.00220.2009.- SMCT1 是短链单羧酸盐的 Na 偶联协同转运蛋白，在结肠、肾皮质和甲状腺等多种上皮细胞的顶膜中表达。我们之前报道过用甜蜜素(-)替代细胞外Cl-可减少SMCT1共转运，并且该蛋白质表现出表面上的阴离子漏电流。在本文中，我们重新审视了小单价阴离子与 SMCT 共转运和漏电流之间的相互作用。我们发现共转运的明显 Cl 依赖性是由于替代阴离子甜蜜素对该蛋白的抑制，而其他几种替代阴离子则充当 SMCT1 的底物；确定了合适的替代阴离子（MES-）。观察到的向外漏电流代表阴离子流入并有利于较大的阴离子（NO3->I->Br->Cl-）；可以观察到超过 1 μA（+50 mV）的电流，并且与高达 100 mM 的阴离子浓度呈现准线性关系。使用 25 mM 碳酸氢盐未产生可测量的泄漏电流。漏电流表现为向外整流，当外部Na+被N-甲基-D-葡萄糖胺(+)取代后，漏电流消失。更准确地说，外部Na+阻断了两个方向的漏电流，但当膜电位变为正值时，其K-i值迅速上升。因此，SMCT1 具有阴离子漏电流，每当外部 Na+ 浓度降低时，该阴离子漏电流就会变得显着。这种漏电流的存在可能代表了 SMCT1 除了共转运短链脂肪酸之外的第二种功能，未来的实验将确定该功能是否在 SMCT1 表达的组织中发挥生理作用。
Coady MJ, Wallendorff B, Bourgeois F, Lapointe J. Anionic leak currents through the Na +/- /monocarboxylate cotransporter SMCT1. Am J Physiol Cell Physiol 298: C124-C131, 2010. First published October 28, 2009; doi:10.1152/ajpcell.00220.2009.- SMCT1 is a Na-coupled cotransporter of short chain monocarboxylates, which is expressed in the apical membrane of diverse epithelia such as colon, renal cortex, and thyroid. We previously reported that SMCT1 cotransport was reduced by extracellular Cl- replacement with cyclamate(-) and that the protein exhibited an ostensible anionic leak current. In this paper, we have revisited the interaction between small monovalent anions and SMCT cotransport and leak currents. We found that the apparent Cl- dependence of cotransport was due to inhibition of this protein by the replacement anion cyclamate, whereas several other replacement anions function as substrates for SMCT1; a suitable replacement anion (MES-) was identified. The observed outward leak currents represented anionic influx and favored larger anions (NO3->I->Br->Cl-); currents in excess of 1 mu A (at +50 mV) could be observed and exhibited a quasilinear relationship with anion concentrations up to 100 mM. Application of 25 mM bicarbonate did not produce measurable leak currents. The leak current displayed outward rectification, which disappeared when external Na+ was replaced by N-methyl-D-glucamine(+). More precisely, external Na+ blocked the leak current in both directions, but its K-i value rose rapidly when membrane potential became positive. Thus SMCT1 possesses a anionic leak current that becomes significant whenever external Na+ concentration is reduced. The presence of this leak current may represent a second function for SMCT1 in addition to cotransporting short chain fatty acids, and future experiments will determine whether this function serves a physiological role in tissues where SMCT1 is expressed.