Li Y X, Rinzel J, Vergara L, Stojilković S S
Mathematical Research Branch, National Institute of Diabetes and Digestive and Kidney Disorders, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biophys J. 1995 Sep;69(3):785-95. doi: 10.1016/S0006-3495(95)79952-0.
Single pituitary cells often fire spontaneous action potentials (APs), which are believed to underlie spiking fluctuations in cytosolic calcium concentration ([Ca2+]i). To address how these basal [Ca2+]i fluctuations depend on changes in plasma membrane voltage (V), simultaneous measurements of V and [Ca2+]i were performed in rat pituitary gonadotrophs. The data show that each [Ca2+]i spike is produced by the Ca2+ entry during a single AP. Using these and previously obtained patch-clamp data, we develop a quantitative mathematical model of this plasma membrane oscillator and the accompanying spatiotemporal [Ca2+]i oscillations. The model demonstrates that AP-induced [Ca2+]i spiking is prominent only in a thin shell layer neighboring the cell surface. This localized [Ca2+]i spike transiently activates the Ca2(+)- dependent K+ current resulting in a sharp afterhyperpolarization following each voltage spike. In accord with experimental observations, the model shows that the frequency and amplitude of the voltage spikes are highly sensitive to current injection and to the blocking of the Ca(2+)-sensitive current. Computations also predict that leaving the membrane channels intact, the firing rate can be modified by changing the Ca2+ handling parameters: the Ca2+ diffusion rate, the Ca2+ buffering capacity, and the plasma membrane Ca2+ pump rate. Finally, the model suggests reasons that spontaneous APs were seen in some gonadotrophs but not in others. This model provides a basis for further exploring how plasma membrane electrical activity is involved in the control of cytosolic calcium level in unstimulated as well as agonist-stimulated gonadotrophs.
单个垂体细胞常自发产生动作电位（APs），人们认为这些动作电位是胞质钙浓度（[Ca2+]i）尖峰波动的基础。为了研究这些基础的[Ca2+]i波动如何依赖于质膜电压（V）的变化，我们在大鼠垂体促性腺激素细胞中同时测量了V和[Ca2+]i。数据表明，每个[Ca2+]i尖峰都是由单个动作电位期间的Ca2+内流产生的。利用这些数据以及先前获得的膜片钳数据，我们建立了这个质膜振荡器以及伴随的时空[Ca2+]i振荡的定量数学模型。该模型表明，动作电位诱导的[Ca2+]i尖峰仅在邻近细胞表面的薄壳层中显著。这种局部的[Ca2+]i尖峰短暂激活Ca2+依赖性钾电流，导致每个电压尖峰后出现明显的超极化后电位。与实验观察结果一致，该模型表明电压尖峰的频率和幅度对电流注入以及Ca2+敏感电流的阻断高度敏感。计算还预测，在膜通道保持完整的情况下，通过改变Ca2+处理参数：Ca2+扩散速率、Ca2+缓冲能力和质膜Ca2+泵速率，可以改变放电频率。最后，该模型揭示了为什么在一些促性腺激素细胞中能看到自发动作电位，而在另一些细胞中却看不到。该模型为进一步探索质膜电活动如何参与未受刺激以及激动剂刺激的促性腺激素细胞中胞质钙水平的控制提供了基础。
