Schools of Biomedicine, University of Manchester, Manchester, UK.
Islets. 2010 Sep-Oct;2(5):303-7. doi: 10.4161/isl.2.5.12748. Epub 2010 Sep 1.
Electrical and secretory activity in the pancreatic β-cell can be elicited by hypotonic cell swelling, due largely to activation of a volume-regulated anion channel (VRAC) leading to depolarisation and electrical activity. However, β-cell responses to cell shrinkage are less well characterised. The present study has examined the effects of osmotic cell shrinkage on rat pancreatic β-cells. Electrical activity and whole-cell current were studied in isolated β-cells using the perforated patch and conventional whole-cell recording techniques. Insulin release was measured using intact islets by radioimmunoassay. Exposure to a 33% hypertonic bath solution resulted in an initial depolarisation and a period of electrical activity. In several cases, this depolarisation was transient and was followed by a hyperpolarisation. A similar pattern was observed with insulin release. In voltage-clamp experiments, osmotic shrinkage resulted in activation of a non-selective cation channel (NSCC) sensitive to inhibition by flufenamic acid and Gd3+. It is suggested that activation of this NSCC is responsible for the depolarisation evoked by hypertonic media. The secondary hyperpolarisation is likely to be the result of inhibition of VRAC activity. These opposing ionic effects could underlie the biphasic effect on insulin release following exposure to hypertonic media.
电和分泌活动在胰岛β细胞可以由低渗细胞肿胀引起，主要是由于激活了体积调节阴离子通道（VRAC）导致去极化和电活动。然而，β细胞对细胞收缩的反应不太清楚。本研究检查了渗透细胞收缩对大鼠胰岛β细胞的影响。使用穿孔贴片和常规全细胞记录技术在分离的β细胞中研究了电活动和全细胞电流。通过放射免疫测定法使用完整的胰岛测量胰岛素释放。暴露于 33%的高渗浴溶液导致初始去极化和一段时间的电活动。在几种情况下，这种去极化是短暂的，随后是超极化。胰岛素释放也观察到类似的模式。在电压钳实验中，渗透收缩导致非选择性阳离子通道（NSCC）的激活，该通道对氟芬那酸和 Gd3+的抑制敏感。据认为，这种 NSCC 的激活是高渗介质引起去极化的原因。继发性超极化可能是 VRAC 活性抑制的结果。这些相反的离子效应可能是暴露于高渗介质后对胰岛素释放产生双相影响的基础。
