Calcium signaling (Santa Clara, Calif.)最新文献

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Calcium Signaling 钙信号

Calcium signaling (Santa Clara, Calif.)

Pub Date : 2020-02-07 DOI: 10.1007/978-3-030-12457-1

M. Islam, J. Bruton, A. Cheng, H. Westerblad

引用次数: 68

The Phase Lag between Agonist-Induced Oscillatory Ca²⁺ and IP₃ Signals Does Not Imply Causality (December 2015). 激动剂诱导的振荡Ca2+和IP3信号之间的相位滞后并不意味着因果关系(2015年12月)。

Calcium signaling (Santa Clara, Calif.)

Pub Date : 2015-12-01

Pei-Chi Yang, M Saleet Jafri

Activated phospholipase C (PLC*) generates 1,4,5-triphosphate (IP₃) and diacylglycerol (DAG) from phosphatidyl inositol (PIP₂). The DAG remains in the plasma membrane and co-activates conventional protein kinase C (PKC) with Ca²⁺. We have developed a mathematical model for the activation of the Ca²⁺-dependent PKC and its negative feedback on phospholipase C (PLC) and coupled it to the De Young-Keizer model for IP₃ mediated Ca²⁺ oscillations. The model describes the cascade of reactions for the translocation of PKC to plasma membrane, and simulates activation of Ca²⁺ and diacylglycerol (DAG) oscillations. The model demonstrates that oscillations in Ca²⁺ and DAG are possible with or without a positive Ca²⁺ feedback on phospholipase C consistent with experiment. In many experimental studies, the timing of the peaks of the Ca²⁺ and IP₃ oscillations have been used to suggest causality, i.e. that the IP₃ oscillations cause the Ca²⁺ oscillations. The model is used to explore this question. To this end, the positive and negative feedback between Ca²⁺ and IP₃ production are modulated, resulting in changes to the phase lag between the peaks in [Ca²⁺]_cyt and [IP]_cyt. The model simulates a possible experimental protocol that can be used to differentiate whether or not the positive feedback of Ca²⁺ on PLC is needed for the oscillations.

活化磷脂酶C (PLC*)从磷脂酰肌醇(PIP2)生成1,4,5-三磷酸(IP3)和二酰基甘油(DAG)。DAG留在质膜内，与Ca2+共同激活常规蛋白激酶C (PKC)。我们建立了Ca2+依赖性PKC的激活及其对磷脂酶C (PLC)的负反馈的数学模型，并将其与IP3介导的Ca2+振荡的De Young-Keizer模型相结合。该模型描述了PKC转运到质膜的级联反应，并模拟了Ca2+和二酰基甘油(DAG)振荡的激活。该模型表明，Ca2+和DAG的振荡是可能的，无论是否有正的Ca2+反馈磷脂酶C与实验一致。在许多实验研究中，Ca2+和IP3振荡的峰值时间已被用来表明因果关系，即IP3振荡引起Ca2+振荡。该模型用于探讨这个问题。为此，Ca2+和IP3产生之间的正负反馈被调制，导致[Ca2+]cyt和[IP]cyt中峰值之间的相位滞后变化。该模型模拟了一种可能的实验方案，该方案可用于区分PLC上Ca2+的正反馈是否需要振荡。

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