A Tale of two receptors

J Theor Biol. 2021 Jun 7:518:110629. doi: 10.1016/j.jtbi.2021.110629. Epub 2021 Feb 17.

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.

Keywords: 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 terms

  • Calcium / metabolism
  • Calcium Signaling*
  • Hepatocytes
  • Humans
  • Phosphorylation
  • Protein Kinase C*
  • Receptors, Purinergic P2Y / metabolism*
  • Signal Transduction
  • Type C Phospholipases* / metabolism

Substances

  • Receptors, Purinergic P2Y
  • Protein Kinase C
  • Type C Phospholipases
  • Calcium