Glucose-stimulated beta-cells exhibit synchronized calcium dynamics across the islet that recruit beta-cells to enhance insulin secretion. Compared to calcium dynamics, the formation and cell-to-cell propagation of electrical signals within the islet are poorly characterized. To determine factors that influence the propagation of electrical activity across the islet underlying calcium oscillations and beta-cell synchronization, we used high-resolution CMOS multielectrode arrays (MEA) to measure voltage changes associated with the membrane potential of individual cells within intact C57BL6 mouse islets. We measured fast (milliseconds, spikes) and slow (seconds, waves) voltage dynamics. Single spike activity and wave signal velocity were both glucose-dependent, but only spike activity was influenced by NMDA receptor activation or inhibition. A repeated glucose stimulus revealed a highly responsive subset of cells in terms of spike activity. When islets were pretreated for 72 hours with glucolipotoxic medium, the wave velocity was significantly reduced. Network analysis confirmed that in response to glucolipotoxicity the synchrony of islet cells was affected due to slower propagating electrical waves and not due to altered spike activity. In summary, this approach provided novel insight regarding the propagation of electrical activity and the disruption of cell-to-cell communication due to excessive stimulation.

中文翻译：

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通过 CMOS 微电极阵列解析胰岛内的时空电信号


葡萄糖刺激的 β 细胞在整个胰岛中表现出同步的钙动力学，募集 β 细胞以增强胰岛素分泌。与钙动力学相比，胰岛内电信号的形成和细胞间传播的表征较差。为了确定影响钙振荡和 β 细胞同步的电活动跨胰岛传播的因素，我们使用高分辨率 CMOS 多电极阵列 （MEA） 来测量与完整 C57BL6 小鼠胰岛内单个细胞的膜电位相关的电压变化。我们测量了快速（毫秒、尖峰）和慢速（秒、波）电压动态。单刺突活性和波信号速度均呈葡萄糖依赖性，但只有刺突活性受 NMDA 受体激活或抑制的影响。重复的葡萄糖刺激揭示了在刺突活性方面高度敏感的细胞亚群。当胰岛用糖脂毒性培养基预处理 72 小时时，波速显著降低。网络分析证实，在糖脂毒性的反应中，胰岛细胞的同步性受到影响是由于电波传播较慢，而不是由于刺突活性改变。总之，这种方法为电活动的传播和由于过度刺激而导致的细胞间通讯中断提供了新的见解。