Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling.

Lens intracellular hydrostatic pressure is generated by the circulation of sodium and modulated by gap junction coupling.
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DOI:
10.1085/jgp.201010538
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发表时间:
2011-06
期刊:
The Journal of general physiology
影响因子:
--
通讯作者:
Mathias RT
Mathias RT
中科院分区:
其他
文献类型:
--
作者:
Gao J;Sun X;Moore LC;White TW;Brink PR;Mathias RT

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最近,我们模拟了通过睫状体色素层和非色素层的缝隙连接通道的流体流动。该模型表明,通道可以运输房水分泌物,但流动将由静水压力而不是渗透驱动。驱动流体通过单层间隙连接所需的压力可能仅为几mmHg,并且难以测量。然而,在透镜中,存在Na+的循环,其可与细胞内液流动耦合。基于这一假设,流体将穿过数百层缝隙连接,这可能需要很大的流体静力梯度。因此,我们使用基于细胞内微电极的压力传感系统测量流体静压作为与透镜中心的距离的函数。在野生型小鼠晶状体中,细胞内压力从中心的1.330 mmHg变化到表面的零。我们有几种敲除/敲入小鼠模型,其具有不同水平的间隙连接通道偶联透镜纤维细胞的表达。来自这些小鼠模型的晶状体中的细胞内流体静压与通道的数量成反比。当透镜的Na+循环被阻断或减少时,中央纤维细胞的细胞内流体静压被消除或成比例地降低。这些数据与我们的假设是一致的:流体循环通过透镜;流体循环的细胞内分支是通过间隙连接通道,并由静水压力驱动;和流体流动产生的膜运输钠。
We recently modeled fluid flow through gap junction channels coupling the pigmented and nonpigmented layers of the ciliary body. The model suggested the channels could transport the secretion of aqueous humor, but flow would be driven by hydrostatic pressure rather than osmosis. The pressure required to drive fluid through a single layer of gap junctions might be just a few mmHg and difficult to measure. In the lens, however, there is a circulation of Na+ that may be coupled to intracellular fluid flow. Based on this hypothesis, the fluid would cross hundreds of layers of gap junctions, and this might require a large hydrostatic gradient. Therefore, we measured hydrostatic pressure as a function of distance from the center of the lens using an intracellular microelectrode-based pressure-sensing system. In wild-type mouse lenses, intracellular pressure varied from ∼330 mmHg at the center to zero at the surface. We have several knockout/knock-in mouse models with differing levels of expression of gap junction channels coupling lens fiber cells. Intracellular hydrostatic pressure in lenses from these mouse models varied inversely with the number of channels. When the lens’ circulation of Na+ was either blocked or reduced, intracellular hydrostatic pressure in central fiber cells was either eliminated or reduced proportionally. These data are consistent with our hypotheses: fluid circulates through the lens; the intracellular leg of fluid circulation is through gap junction channels and is driven by hydrostatic pressure; and the fluid flow is generated by membrane transport of sodium.
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