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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >HYPERTONICITY ACTIVATES NONSELECTIVE CATION CHANNELS IN MOUSE CORTICAL COLLECTING DUCT CELLS
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HYPERTONICITY ACTIVATES NONSELECTIVE CATION CHANNELS IN MOUSE CORTICAL COLLECTING DUCT CELLS

机译:高渗性在小鼠皮质收集导管细胞中激活非选择性阳离子通道

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We investigated the effect of cell shrinkage on whole-cell currents of M-1 mouse cortical collecting duct cells. Addition of 100 mM sucrose to an isotonic NaCl bath solution induced cell shrinkage and increased whole-cell currents within 5-10 min by approximate to 12-fold. The effect was reversible upon return to isotonic solution and could also be elicited by adding 100 mM urea or 50 mM NaCl. Replacement of hath Na+ by K+, Cs+, Li+, or Rb+ did not significantly affect the stimulated inward current, but replacement by N-methyl-D-glucamine reduced it by 88.1 +/- 1.3% (n = 34); this demonstrates that hypertonicity activates a nonselective alkali cation conductance. The activation was independent of extra- and intracellular Ca2+, but 1 or 10 mM ATP in the pipette suppressed it in a concentration-dependent manner, indicating that intracellular ATP levels may modulate the degree of channel activation. Flufenamic acid (0.1 mM) and gadolinium (0.1 mM) inhibited the stimulated current by 68.7 +/- 5.9% (n = 9) and 32.4 +/- 11.7% (n = 6), respectively, whereas 0.1 mM amiloride had no significant effect. During the early phase of hypertonic stimulation single-channel transitions could be detected in whole cell current recordings, and a gradual activation of 30 and more individual channels with a single-channel conductance of 26.7 +/- 0.4 pS (n = 29) could be resolved. Thus, we identified the nonselective cation channel underlying the shrinkage-induced whole-cell conductance that may play a role in volume regulation. [References: 34]
机译:我们调查了细胞收缩对M-1小鼠皮质收集导管细胞全细胞电流的影响。将100 mM蔗糖添加到等渗的NaCl浴溶液中会诱导细胞收缩,并在5-10分钟内使全细胞电流增加约12倍。返回等渗溶液后效果是可逆的,也可以通过添加100 mM尿素或50 mM NaCl引发。用K +,Cs +,Li +或Rb +代替hath Na +不会显着影响受激内向电流,但是用N-甲基-D-葡糖胺替代可将其降低88.1 +/- 1.3%(n = 34)。这表明高渗性激活了非选择性碱金属阳离子电导。激活与细胞外和细胞内Ca2 +无关,但是移液管中1或10 mM ATP以浓度依赖的方式抑制了它,表明细胞内ATP水平可能调节通道激活的程度。氟芬那酸(0.1 mM)和g(0.1 mM)分别将受激电流抑制68.7 +/- 5.9%(n = 9)和32.4 +/- 11.7%(n = 6),而0.1 mM阿米洛利则无显着性影响。在高渗刺激的早期阶段,可以在全细胞电流记录中检测到单通道转变,并且可以逐步激活30个及更多的单个通道,单通道电导为26.7 +/- 0.4 pS(n = 29)。解决。因此,我们确定了收缩诱导的全细胞电导的潜在非选择性阳离子通道,该通道可能在体积调节中起作用。 [参考:34]

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