Wang S S, Alousi A A, Thompson S H
Neurosciences Program, Stanford University, Pacific Grove, California 93950, USA.
J Gen Physiol. 1995 Jan;105(1):149-71. doi: 10.1085/jgp.105.1.149.
In many eukaryotic cell types, receptor activation leads to the formation of inositol 1,4,5-trisphosphate (IP3) which causes calcium ions (Ca) to be released from internal stores. Ca release was observed in response to the muscarinic agonist carbachol by fura-2 imaging of N1E-115 neuroblastoma cells. Ca release followed receptor activation after a latency of 0.4 to 20 s. Latency was not caused by Ca feedback on IP3 receptors, but rather by IP3 accumulation to a threshold for release. The dependence of latency on carbachol dose was fitted to a model in which IP3 synthesis and degradation compete, resulting in gradual accumulation to a threshold level at which Ca release becomes regenerative. This analysis gave degradation rate constants of IP3 in single cells ranging from 0 to 0.284 s-1 (0.058 +/- 0.067 s-1 SD, 53 cells) and a mean IP3 lifetime of 9.2 +/- 2.2 s. IP3 degradation was also measured directly with biochemical methods. This gave a half life of 9 +/- 2 s. The rate of IP3 degradation sets the time frame over which IP3 accumulations are integrated as input signals. IP3 levels are also filtered over time, and on average, large-amplitude oscillations in IP3 in these cells cannot occur with period < 10 s.
在许多真核细胞类型中，受体激活会导致肌醇1,4,5 -三磷酸（IP3）的形成，进而使钙离子（Ca）从细胞内储存库中释放出来。通过用fura - 2对N1E - 115神经母细胞瘤细胞进行成像，观察到毒蕈碱激动剂卡巴胆碱可引发Ca释放。Ca释放在受体激活后延迟0.4至20秒出现。延迟并非由Ca对IP3受体的反馈引起，而是由IP3积累至释放阈值所致。延迟对卡巴胆碱剂量的依赖性符合一个模型，其中IP3的合成与降解相互竞争，导致其逐渐积累至阈值水平，此时Ca释放变为再生性的。该分析得出单个细胞中IP3的降解速率常数范围为0至0.284 s⁻¹（0.058 ± 0.067 s⁻¹标准差，53个细胞），IP3的平均寿命为9.2 ± 2.2秒。IP3降解也通过生化方法直接测定，得出半衰期为9 ± 2秒。IP3降解速率设定了IP3积累作为输入信号进行整合的时间框架。随着时间推移，IP3水平也会被过滤，并且平均而言，这些细胞中IP3的大幅度振荡周期不可能小于10秒。
