Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School Rutgers, The State University of New Jersey, Newark, NJ 07103, United States.
J Theor Biol. 2021 Jun 7;518:110629. doi: 10.1016/j.jtbi.2021.110629. Epub 2021 Feb 17.
Calcium (Ca) oscillations in hepatocytes have a wide dynamic range. In particular, recent experimental evidence shows that agonist stimulation of the P2Y family of receptors leads to qualitatively diverse Ca oscillations. We present a new model of Ca oscillations in hepatocytes based on these experiments to investigate the mechanisms controlling P2Y-activated Ca oscillations. The model accounts for Ca regulation of the IP receptor (IPR), the positive feedback from Ca on phospholipase C (PLC) and the P2Y receptor phosphorylation by protein kinase C (PKC). Furthermore, PKC is shown to control multiple cellular substrates. Utilising the model, we suggest the activity and intensity of PLC and PKC necessary to explain the qualitatively diverse Ca oscillations in response to P2Y receptor activation.
肝细胞中的钙（Ca）振荡具有广泛的动态范围。特别是，最近的实验证据表明，激动剂刺激 P2Y 家族受体可导致 Ca 振荡的定性多样性。我们基于这些实验提出了一个新的肝细胞 Ca 振荡模型，以研究控制 P2Y 激活 Ca 振荡的机制。该模型考虑了 Ca 对 IP 受体（IPR）的调节、Ca 对磷脂酶 C（PLC）的正反馈以及蛋白激酶 C（PKC）对 P2Y 受体的磷酸化。此外，还表明 PKC 控制多种细胞底物。利用该模型，我们提出了 PLC 和 PKC 的活性和强度，以解释对 P2Y 受体激活的响应中 Ca 振荡的定性多样性。
