A Tale of two receptors.

• 影响指数: 2.405
• 发表时间: 06 2021 7
• 来源期刊: J Theor Biol
• DOI: 10.1016/j.jtbi.2021.110629
• PMID: 33607144
• 文章类型: Journal Article
• 中科院分区: Q2;Q1
• 作者列表: Cloete I,Corrêa-Velloso JC,Bartlett PJ,Kirk V,Thomas AP,Sneyd J

关键词: IP(3); IP(3) receptors; Models of calcium oscillations; P2Y receptors; Phospholipase C (PLC); Protein Kinase C (PKC); Purinergic receptors; Receptor phosphorylation; Signal transduction

Mesh: Calcium / metabolism; Calcium Signaling; Hepatocytes; Humans; Phosphorylation; Protein Kinase C; Receptors, Purinergic P2Y / metabolism; Signal Transduction; Type C Phospholipases / metabolism

Abstract

Calcium (Ca2+) 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 Ca2+ oscillations. We present a new model of Ca2+ oscillations in hepatocytes based on these experiments to investigate the mechanisms controlling P2Y-activated Ca2+ oscillations. The model accounts for Ca2+ regulation of the IP3 receptor (IP3R), the positive feedback from Ca2+ 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 Ca2+ oscillations in response to P2Y receptor activation.