TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct
TRPV4 as a flow sensor in flow-dependent K+ secretion from the cortical collecting duct
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DOI：
10.1152/ajprenal.00458.2005
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发表时间：
2007-02-01
影响因子：
4.2
通讯作者：
Suzuki, Makoto
中科院分区：
文献类型：
--
作者：
Taniguchi, Junichi;Tsuruoka, Shuichi;Suzuki, Makoto
瞬时受体香草酸-4(TRPV4)是一种机械敏感、肿胀激活的阳离子通道，广泛存在于肾远端小管中。然而，对于TRPV4是否沿着根尖和/或基底外侧膜表达，免疫定位研究提供了相互矛盾的数据。为了揭示TRPV4在体内远端小管K+流动依赖性分泌中的作用，采用体外微灌流技术，测定了TRPV4(+/+)和TRPV4(-/-)小鼠尿K+排泄量和皮质集合管K+、Na+的净转运。从TRPV4(+/+)小鼠分离的CCDs的K+净分泌量和Na+重吸收均呈流量依赖性增加，而腔内应用TRPV4激动剂M4α-佛波醇-12，13-十二酸(4αPDD)可显著增强这一作用。在TRPV4(+/+)小鼠，未观察到K+和Na+净转运的流量依赖性，也没有观察到4αPDD对CCDs的影响。4αPDD对TRPV4(+/+)CCDs的离子转运几乎没有影响，而腔内给药对这些离子转运的影响较小。静脉应用速尿刺激尿量时，TRPV4(-/-)小鼠的尿钾排泄量显著低于TRPV4(-/-)小鼠。这些观察表明，腔内或基底外侧膜上的TRPV4通道作为流量传感器在小鼠CCDS的流量依赖性K+分泌机制中起着重要作用。
The transient receptor vanilloid-4 (TRPV4) is a mechanosensitive, swell-activated cation channel that is abundant in the renal distal tubules. Immunolocalization studies, however, present conflicting data as to whether TRPV4 is expressed along the apical and/or basolateral membranes. To disclose the role of TRPV4 in flow-dependent K+ secretion in distal tubules in vivo, urinary K+ excretion and net transports of K+ and Na+ in the cortical collecting duct (CCD) were measured with an in vitro microperfusion technique in TRPV4(+/+) and TRPV4(-/-) mice. Both net K+ secretion and Na+ reabsorption were flow dependently increased in the CCDs isolated from TRPV4(+/+) mice, which were significantly enhanced by a luminal application of 50 mu M 4 alpha-phorbol-12,13-didecanoate (4 alpha PDD), an agonist of TRPV4. No flow dependence of net K+ and Na+ transports or effects of 4 alpha PDD on CCDs were observed in TRPV4(+/+) mice. A basolateral application of 4 alpha PDD had little effect on these ion transports in the TRPV4(+/+) CCDs, while the luminal application did. Urinary K+ excretion was significantly smaller in TRPV4(-/-) than in TRPV4(-/-) mice when urine production was stimulated by a venous application of furosemide. These observations suggested an essential role of the TRPV4 channels in the luminal or basolateral membrane as flow sensors in the mechanism underlying the flow-dependent K+ secretion in mouse CCDs.