New saliva secretion model based on the expression of Na+-K+ pump and K+ channels in the apical membrane of parotid acinar cells

New saliva secretion model based on the expression of Na+-K+ pump and K+ channels in the apical membrane of parotid acinar cells
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DOI:
10.1007/s00424-018-2109-0
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发表时间:
2018-04-01
影响因子:
4.5
通讯作者:
Nanasi, Peter P.
Nanasi, Peter P.
中科院分区:
医学3区
文献类型:
--
作者:
Almassy, Janos;Siguenza, Elias;Nanasi, Peter P.

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腮腺腺泡细胞的质膜在功能上分为顶侧和基底侧两个区域。根据目前的模型,液体分泌是由跨上皮离子梯度驱动的,这有助于水通过渗透从肺泡进入腺泡腔。渗透梯度是由顶端Cl-流出和随后的细胞旁Na+转运产生的。在该模型中,Na+-K+泵仅位于基底外侧膜中,并且在唾液分泌中具有重要作用,因为通过基底外侧Na+-K+-2Cl(-)共转运的Cl-转运的驱动力是由Na+-K+泵产生的。此外,在腺泡细胞刺激过程中Cl-流动的连续电化学梯度由基底外侧K+流出维持。然而,使用单细胞电生理学和Ca 2+成像的组合,我们证明,靠近腮腺腺泡细胞的顶膜的Ca 2+的光解触发了显着的K+电流,表明大量的K+分泌到腔在刺激过程中。然而,初级唾液的K+含量相对较低,这表明K+可能通过顶端膜被重吸收。因此,我们研究了腺泡细胞中Na+-K+泵的定位。我们发现,泵出现均匀分布在整个质膜,包括细胞的顶端。基于这些结果,提出了一个新的唾液分泌的数学模型,其中泵从管腔重吸收K+并向管腔分泌Na+,这可以部分地补充细胞旁Na+途径。
The plasma membrane of parotid acinar cells is functionally divided into apical and basolateral regions. According to the current model, fluid secretion is driven by transepithelial ion gradient, which facilitates water movement by osmosis into the acinar lumen from the interstitium. The osmotic gradient is created by the apical Cl- efflux and the subsequent paracellular Na+ transport. In this model, the Na+-K+ pump is located exclusively in the basolateral membrane and has essential role in salivary secretion, since the driving force for Cl- transport via basolateral Na+-K+-2Cl(-) cotransport is generated by the Na+-K+ pump. In addition, the continuous electrochemical gradient for Cl- flow during acinar cell stimulation is maintained by the basolateral K+ efflux. However, using a combination of single-cell electrophysiology and Ca2+-imaging, we demonstrate that photolysis of Ca2+ close to the apical membrane of parotid acinar cells triggered significant K+ current, indicating that a substantial amount of K+ is secreted into the lumen during stimulation. Nevertheless, the K+ content of the primary saliva is relatively low, suggesting that K+ might be reabsorbed through the apical membrane. Therefore, we investigated the localization of Na+-K+ pumps in acinar cells. We show that the pumps appear evenly distributed throughout the whole plasma membrane, including the apical pole of the cell. Based on these results, a new mathematical model of salivary fluid secretion is presented, where the pump reabsorbs K+ from and secretes Na+ to the lumen, which can partially supplement the paracellular Na+ pathway.