A Tale of two receptors.

Authors :: Cloete I
Corrêa-Velloso JC
Bartlett PJ
Kirk V
Thomas AP
Sneyd J
Source :: Journal of theoretical biology [J Theor Biol] 2021 Jun 07; Vol. 518, pp. 110629. Date of Electronic Publication: 2021 Feb 17.
Publication Year :: 2021
Abstract: Calcium (Ca <superscript>2+</superscript> ) 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 <superscript>2+</superscript> oscillations. We present a new model of Ca <superscript>2+</superscript> oscillations in hepatocytes based on these experiments to investigate the mechanisms controlling P2Y-activated Ca <superscript>2+</superscript> oscillations. The model accounts for Ca <superscript>2+</superscript> regulation of the IP <subscript>3</subscript> receptor (IP <subscript>3</subscript> R), the positive feedback from Ca <superscript>2+</superscript> 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 <superscript>2+</superscript> oscillations in response to P2Y receptor activation.<br /> (Copyright © 2021 Elsevier Ltd. All rights reserved.)