A Tale of two receptors

Ielyaas Cloete; Juliana C Corrêa-Velloso; Paula J Bartlett; Vivien Kirk; Andrew P Thomas; James Sneyd

doi:10.1016/j.jtbi.2021.110629

A Tale of two receptors

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

Authors

Ielyaas Cloete¹, Juliana C Corrêa-Velloso², Paula J Bartlett², Vivien Kirk¹, Andrew P Thomas², James Sneyd¹

Affiliations

¹ Department of Mathematics, University of Auckland, Auckland 1142, New Zealand.
² Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School Rutgers, The State University of New Jersey, Newark, NJ 07103, United States.

PMID: 33607144
DOI: 10.1016/j.jtbi.2021.110629

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