Roper Peter, Callaway Joseph, Armstrong William
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 2004 May 19;24(20):4818-31. doi: 10.1523/JNEUROSCI.4203-03.2004.
Vasopressin secreting neurons of the rat hypothalamus discharge lengthy, repeating bursts of action potentials in response to physiological stress. Although many electrical currents and calcium-dependent processes have been isolated and analyzed in these cells, their interactions are less well fathomed. In particular, the mechanism of how each burst is triggered, sustained, and terminated is poorly understood. We present a mathematical model for the bursting mechanism, and we support our model with new simultaneous electrical recording and calcium imaging data. We show that bursts can be initiated by spike-dependent calcium influx, and we propose that the resulting elevation of bulk calcium inhibits a persistent potassium current. This inhibition depolarizes the cell above threshold and so triggers regenerative spiking and further calcium influx. We present imaging data to show that bulk calcium reaches a plateau within the first few seconds of the burst, and our model indicates that this plateau occurs when calcium influx is balanced by efflux and uptake into stores. We conjecture that the burst is terminated by a slow, progressive desensitization to calcium of the potassium leak current. Finally, we propose that the opioid dynorphin, which is known to be secreted from the somatodendritic region and has been shown previously to regulate burst length and phasic activity in these cells, is the autocrine messenger for this desensitization.
大鼠下丘脑分泌血管加压素的神经元在生理应激时会发放长时间的、重复的动作电位爆发。尽管在这些细胞中已经分离并分析了许多电流和钙依赖性过程,但它们之间的相互作用还了解得较少。特别是,每次爆发是如何触发、维持和终止的机制还知之甚少。我们提出了一种关于爆发机制的数学模型,并用新的同步电记录和钙成像数据来支持我们的模型。我们表明爆发可以由与动作电位相关的钙内流引发,并且我们提出由此导致的胞内钙浓度升高会抑制一种持续的钾电流。这种抑制会使细胞去极化至阈值以上,从而触发再生性动作电位发放和进一步的钙内流。我们展示的成像数据表明,胞内钙在爆发的最初几秒内达到一个平台期,并且我们的模型表明当钙内流与外流以及进入储存库的摄取达到平衡时就会出现这个平台期。我们推测爆发是由钾泄漏电流对钙的缓慢、渐进性脱敏作用所终止的。最后,我们提出阿片类物质强啡肽,已知它从树突体区域分泌,并且先前已被证明可调节这些细胞中的爆发长度和相位活动,是这种脱敏作用的自分泌信使。