Bertram R, Previte J, Sherman A, Kinard T A, Satin L S
School of Science, Pennsylvania State University, Erie, Pennsylvania 16563, USA.
Biophys J. 2000 Dec;79(6):2880-92. doi: 10.1016/S0006-3495(00)76525-8.
Pancreatic beta-cells exhibit bursting oscillations with a wide range of periods. Whereas periods in isolated cells are generally either a few seconds or a few minutes, in intact islets of Langerhans they are intermediate (10-60 s). We develop a mathematical model for beta-cell electrical activity capable of generating this wide range of bursting oscillations. Unlike previous models, bursting is driven by the interaction of two slow processes, one with a relatively small time constant (1-5 s) and the other with a much larger time constant (1-2 min). Bursting on the intermediate time scale is generated without need for a slow process having an intermediate time constant, hence phantom bursting. The model suggests that isolated cells exhibiting a fast pattern may nonetheless possess slower processes that can be brought out by injecting suitable exogenous currents. Guided by this, we devise an experimental protocol using the dynamic clamp technique that reliably elicits islet-like, medium period oscillations from isolated cells. Finally, we show that strong electrical coupling between a fast burster and a slow burster can produce synchronized medium bursting, suggesting that islets may be composed of cells that are intrinsically either fast or slow, with few or none that are intrinsically medium.
胰腺β细胞呈现出具有广泛周期范围的爆发式振荡。在分离的细胞中，周期通常为几秒或几分钟，而在完整的胰岛中，周期处于中间范围（10 - 60秒）。我们开发了一个用于β细胞电活动的数学模型，该模型能够产生这种广泛范围的爆发式振荡。与之前的模型不同，爆发是由两个缓慢过程的相互作用驱动的，一个具有相对较小的时间常数（1 - 5秒），另一个具有大得多的时间常数（1 - 2分钟）。在中间时间尺度上的爆发无需具有中间时间常数的缓慢过程即可产生，即虚拟爆发。该模型表明，表现出快速模式的分离细胞可能仍然具有可以通过注入合适的外源电流而显现出来的较慢过程。以此为指导，我们设计了一种使用动态钳技术的实验方案，该方案能够可靠地从分离细胞中引发类似胰岛的中等周期振荡。最后，我们表明快速爆发细胞与缓慢爆发细胞之间的强电耦合可以产生同步的中等爆发，这表明胰岛可能由本质上快速或缓慢的细胞组成，很少或没有本质上处于中间状态的细胞。
