Best Len, Brown Peter D
School of Medicine, Manchester Royal Infirmary, University of Manchester, Oxford Road, Manchester M139WL, UK.
J Membr Biol. 2009 Jul;230(2):83-91. doi: 10.1007/s00232-009-9189-x. Epub 2009 Aug 8.
There is evidence that depolarization of the pancreatic beta cell by glucose involves cell swelling and activation of the volume-regulated anion channel (VRAC). However, it is unclear whether cell swelling per se or accompanying changes in intracellular osmolality and/or ionic strength are responsible for VRAC activation. VRAC activity was measured in rat beta cells by conventional or perforated patch whole-cell recording. Cell volume was measured by video imaging. In conventional whole-cell recordings, VRAC activation was achieved by exposure of the cells to a hyposmotic bath solution, by application of positive pressure to the pipette, or by use of a hyperosmotic pipette solution. Increased concentrations of intracellular CsCl also caused channel activation, but with delayed kinetics. In perforated patch recordings, VRAC activation was induced by isosmotic addition of the permeable osmolytes urea, 3-O-methyl glucose, arginine, and NH4Cl. These effects were all accompanied by beta-cell swelling. It is concluded that increased cell volume, whether accompanied by raised intracellular osmolality or ionic strength, is a major determinant of VRAC activation in the beta cell. However, increased intracellular ionic strength markedly reduced the rate of VRAC activation. These findings are consistent with the hypothesis that the accumulation of glucose metabolites in the beta cell, and the resultant increase in cell volume, provides a signal coupling glucose metabolism with VRAC activation.
有证据表明，葡萄糖使胰腺β细胞去极化涉及细胞肿胀以及容积调节性阴离子通道（VRAC）的激活。然而，尚不清楚是细胞肿胀本身还是伴随的细胞内渗透压和/或离子强度变化导致了VRAC的激活。通过传统的或穿孔膜片钳全细胞记录法测量大鼠β细胞中的VRAC活性。通过视频成像测量细胞体积。在传统的全细胞记录中，通过将细胞暴露于低渗浴液、向移液管施加正压或使用高渗移液管溶液来实现VRAC的激活。细胞内CsCl浓度的增加也会导致通道激活，但动力学延迟。在穿孔膜片钳记录中，通过等渗添加可渗透的渗透剂尿素、3 - O - 甲基葡萄糖、精氨酸和NH4Cl来诱导VRAC激活。所有这些效应都伴随着β细胞肿胀。得出的结论是，细胞体积增加，无论是否伴随着细胞内渗透压或离子强度升高，都是β细胞中VRAC激活的主要决定因素。然而，细胞内离子强度的增加显著降低了VRAC激活的速率。这些发现与以下假设一致，即β细胞中葡萄糖代谢产物的积累以及由此导致的细胞体积增加，提供了一个将葡萄糖代谢与VRAC激活相耦合的信号。
