SLC4A11 is an EIPA-sensitive Na+ permeable pHi regulator
SLC4A11 is an EIPA-sensitive Na+ permeable pHi regulator
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DOI：
10.1152/ajpcell.00056.2013
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发表时间：
2013-10-01
影响因子：
5.5
通讯作者：
Bonanno, Joseph A.
中科院分区：
文献类型：
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作者：
Ogando, Diego G.;Jalimarada, Supriya S.;Bonanno, Joseph A.
Slc 4a 11是溶质连接共转运蛋白4家族的成员，主要由碳酸氢盐转运蛋白组成，被描述为产电的2Na（+）-B（OH）（4）（-）（硼酸盐）共转运蛋白和Na+-2OH（-）共转运蛋白。本研究的目的是确认和/或阐明SLC 4A 11的功能。在用SLC 4 A11转染的HEK 293细胞中，我们检测了SLC 4 A11是否是：1）Na+-HCO 3-共转运蛋白，2）Na+-OH-（H+）转运蛋白，和/或3）Na+-B（OH）（4）（-）共转运蛋白。与对照细胞相比，CO2/HCO 3灌注在SLC 4A 11转染的细胞中pH（i）变化或Na+通量的速率或程度上没有显著差异。同样，在CO2/HCO 3-中，对照和转染的SLC 4A 11之间在Na+去除上的酸化和在Na+添加回上的碱化没有显著差异，表明SLC 4A 11不具有Na+-HCO 3-共转运活性。在不存在CO2/HCO 3-的情况下，SLC 4A 11转染的细胞显示出较高的静息细胞内Na+浓度（[Na+]（i）; 25 vs. 17 mM），增加的NH 4+诱导的酸化和增加的NH 4脉冲后的酸回收率（160%）。Na+去除和加回后，Na+流出和流入分别更快（80%），表明SLC 4A 11的Na+-OH-（H+）转运。在NHE缺陷型PS120细胞中证实了碱化恢复增加，表明SLC 4A 11是真正的Na+-OH-（H+）转运蛋白，而不是NHE的激活剂。SLC 4A 11介导的H+外排受5-（N-乙基-N-异丙基）阿米洛利（EIPA; EC 50：0.1 μ M）抑制。在SLC 4A 11转染的细胞中，在无Na+脉冲期间，10 mM硼酸盐的存在不会改变dpH（i）/dt或Δ pH。总之，我们的结果表明，SLC 4A 11不是碳酸氢盐或硼酸盐连接的转运蛋白，但具有显著的EIPA敏感性Na+-OH-（H+）和NH 4+渗透性。
Slc4a11, a member of the solute linked cotransporter 4 family that is comprised predominantly of bicarbonate transporters, was described as an electrogenic 2Na(+)-B(OH)(4)(-) (borate) cotransporter and a Na+-2OH(-) cotransporter. The goal of the current study was to confirm and/or clarify the function of SLC4A11. In HEK293 cells transfected with SLC4A11 we tested if SLC4A11 is a: 1) Na+-HCO3- cotransporter, 2) Na+-OH-(H+) transporter, and/or 3) Na+-B(OH)(4)(-) cotransporter. CO2/HCO3- perfusion yielded no significant differences in rate or extent of pH(i) changes or Na+ flux in SLC4A11-transfected compared with control cells. Similarly, in CO2/HCO3-, acidification on removal of Na+ and alkalinization on Na+ add back were not significantly different between control and transfected indicating that SLC4A11 does not have Na+-HCO3- cotransport activity. In the absence of CO2/HCO3-, SLC4A11-transfected cells showed higher resting intra-celllular Na+ concentration ([Na+](i); 25 vs. 17 mM), increased NH4+-induced acidification and increased acid recovery rate (160%) after an NH4 pulse. Na+ efflux and influx were faster (80%) following Na+ removal and add back, respectively, indicative of Na+-OH-(H+) transport by SLC4A11. The increased alkalinization recovery was confirmed in NHE-deficient PS120 cells demonstrating that SLC4A11 is a bonafide Na+-OH-(H+) transporter and not an activator of NHEs. SLC4A11-mediated H+ efflux is inhibited by 5-(N-ethyl-N-isopropyl) amiloride (EIPA; EC50: 0.1 mu M). The presence of 10 mM borate did not alter dpH(i)/dt or Delta pH during a Na+-free pulse in SLC4A11-transfected cells. In summary our results show that SLC4A11 is not a bicarbonate or borate-linked transporter but has significant EIPA-sensitive Na+-OH-(H+) and NH4+ permeability.