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人合体滋养层细胞中的大氯通道:胎盘容量调节中牛磺酸外流的一条途径?

The maxi-chloride channel in human syncytiotrophoblast: a pathway for taurine efflux in placental volume regulation?

作者信息

Vallejos C, Riquelme G

机构信息

Laboratorio de Electrofisiología de Membranas, Programa de Fisiología y Biofísica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Casilla 70005, Santiago 7, Chile.

出版信息

Placenta. 2007 Nov-Dec;28(11-12):1182-91. doi: 10.1016/j.placenta.2007.06.005. Epub 2007 Aug 6.

Abstract

Taurine (Tau), the most abundant amino acid in fetal blood, is highly concentrated in human placenta. During pregnancy, Tau is involved in the neurological development of the fetus, and in volume regulation of the placenta. The placenta may release taurine in parallel with K(+) and Cl(-) in response to an increase in cell volume. However, the pathway for the volume-activated taurine efflux is unknown. One candidate is a voltage-dependent Maxi-chloride channel from apical syncytiotrophoblast membrane (MVM), with a conductance over 200pS and multiple subconductance states. Our aim was to study whether this channel could be a Tau conductive pathway in the MVM. Purified human placental MVM were reconstituted into giant liposomes suitable for patch clamp recordings. Typical Maxi-chloride channel activity was detected in symmetrical chloride (Cl(-)) solutions, and then taurine (Tau), Aspartate (Asp), and glutamate (Glu) solutions were used in the bath of excised patches to detect single channel currents carried by these anions. The relative permeabilities (P), estimated from the shift in reversal potential of current-voltage curves after anion replacement, were as follows: Chloride>Taurine=Glutamate=Aspartate. In Tau symmetric conditions using equivalent Cl(-) concentrations, the slope conductance was 62.4+/-7.3pS. The data shows that Tau and other amino acids diffuse through the Maxi-chloride channel, which could be of great importance as part of the mechanism involved in the volume regulation process in human placenta.

摘要

牛磺酸(Tau)是胎儿血液中含量最丰富的氨基酸,在人胎盘中高度浓缩。在怀孕期间,牛磺酸参与胎儿的神经发育以及胎盘的容量调节。胎盘可能会在细胞体积增加时与钾离子(K⁺)和氯离子(Cl⁻)同时释放牛磺酸。然而,容量激活的牛磺酸外流途径尚不清楚。一种可能的途径是来自顶端合体滋养层细胞膜(MVM)的电压依赖性大氯离子通道,其电导超过200pS且具有多种亚电导状态。我们的目的是研究该通道是否可能是MVM中牛磺酸的传导途径。将纯化的人胎盘MVM重组成适合膜片钳记录的巨型脂质体。在对称的氯化物(Cl⁻)溶液中检测到典型的大氯离子通道活性,然后在切除膜片的浴槽中使用牛磺酸(Tau)、天冬氨酸(Asp)和谷氨酸(Glu)溶液来检测这些阴离子携带的单通道电流。根据阴离子置换后电流 - 电压曲线反转电位的变化估算的相对渗透率(P)如下:氯离子>牛磺酸 = 谷氨酸 = 天冬氨酸。在使用等效Cl⁻浓度的牛磺酸对称条件下,斜率电导为62.4±7.3pS。数据表明,牛磺酸和其他氨基酸通过大氯离子通道扩散,这可能作为人胎盘容量调节过程所涉及机制的一部分具有重要意义。

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