Molecular Identification and Physiological Roles of Parotid Acinar Cell Maxi-K Channels*

Molecular Identification and Physiological Roles of Parotid Acinar Cell Maxi-K Channels*
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DOI:
10.1074/jbc.m603871200
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发表时间:
2006-09
影响因子:
4.8
通讯作者:
V. Romanenko;T. Nakamoto;A. Srivastava;J. E. Melvin;T. Begenisich
V. Romanenko;T. Nakamoto;A. Srivastava;J. E. Melvin;T. Begenisich
中科院分区:
生物学2区
文献类型:
--
作者:
V. Romanenko;T. Nakamoto;A. Srivastava;J. E. Melvin;T. Begenisich

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液体分泌组织的生理成功依赖于Ca 2+激活的Cl-和K+通道之间的调节相互作用。腮腺腺泡细胞表达两种类型的Ca 2+激活的K+通道:中等电导IK 1通道和最大K通道。IK 1通道由KCa3.1基因编码,KCa1.1基因可能是最大K通道的候选基因。为了确认maxi-K通道的遗传特性并探索其特定作用,我们研究了KCa1.1基因消融的小鼠腮腺。这些动物的腮腺腺泡细胞缺乏maxi-K通道,证实了它们的遗传特性。刺激腮腺液分泌率正常,但分泌液的钠和钾含量改变。此外,我们发现,在腺泡细胞的调节体积减少KCa1.1-null动物大大受损。我们研究了两种K+通道基因缺失的动物的液体分泌。分泌速率严重降低,分泌液的离子含量显著改变。我们测量了腺泡细胞的膜电位从野生型小鼠和动物与一个或两个K+通道基因消融。他们揭示了观察到的对液体分泌的功能影响反映了细胞膜电压的改变。我们的研究结果表明,最大-K通道是至关重要的,在这些细胞的监管量减少,他们发挥了重要的作用,在这些液体分泌唾液腺的导管中的钠吸收和钾分泌过程。
The physiological success of fluid-secreting tissues relies on a regulated interplay between Ca2+-activated Cl– and K+ channels. Parotid acinar cells express two types of Ca2+-activated K+ channels: intermediate conductance IK1 channels and maxi-K channels. The IK1 channel is encoded by the KCa3.1 gene, and the KCa1.1 gene is a likely candidate for the maxi-K channel. To confirm the genetic identity of the maxi-K channel and to probe its specific roles, we studied parotid glands in mice with the KCa1.1 gene ablated. Parotid acinar cells from these animals lacked maxi-K channels, confirming their genetic identity. The stimulated parotid gland fluid secretion rate was normal, but the sodium and potassium content of the secreted fluid was altered. In addition, we found that the regulatory volume decrease in acinar cells was substantially impaired in KCa1.1-null animals. We examined fluid secretion from animals with both K+ channel genes deleted. The secretion rate was severely reduced, and the ion content of the secreted fluid was significantly changed. We measured the membrane potentials of acinar cells from wild-type mice and from animals with either or both K+ channel genes ablated. They revealed that the observed functional effects on fluid secretion reflected alterations in cell membrane voltage. Our findings show that the maxi-K channels are critical for the regulatory volume decrease in these cells and that they play an important role in the sodium uptake and potassium secretion process in the ducts of these fluid-secreting salivary glands.