Tags

Type your tag names separated by a space and hit enter

Dual mechanisms of Ca2+ oscillations in hepatocytes.
J Theor Biol. 2020 Oct 21; 503:110390.JT

Abstract

Calcium (Ca2+) oscillations in hepatocytes control many critical cellular functions, including glucose metabolism and bile secretion. The mechanisms underlying repetitive Ca2+ oscillations and how these mechanisms regulate these oscillations is not fully understood. Recent experimental evidence has shown that both Ca2+ regulation of the inositol 1,4,5-trisphosphate (IP3) receptor and IP3 metabolism generate Ca2+ oscillations and co-exist in hepatocytes. To investigate the effects of these feedback mechanisms on the Ca2+ response, we construct a mathematical model of the Ca2+ signalling network in hepatocytes. The model accounts for the biphasic regulation of Ca2+ on the IP3 receptor (IP3R) and the positive feedback from Ca2+ on IP3 metabolism, via activation of phospholipase C (PLC) by agonist and Ca2+. Model simulations show that Ca2+ oscillations exist for both constant [IP3] and for [IP3] changing dynamically. We show, both experimentally and in the model, that as agonist concentration increases, Ca2+ oscillations transition between simple narrow-spike oscillations and complex broad-spike oscillations. The model predicts that narrow-spike oscillations persist when Ca2+ transport across the plasma membrane is blocked. This prediction has been experimentally validated. In contrast, broad-spike oscillations are terminated when plasma membrane transport is blocked. We conclude that multiple feedback mechanisms participate in regulating Ca2+ oscillations in hepatocytes.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32628939

Citation

Cloete, Ielyaas, et al. "Dual Mechanisms of Ca2+ Oscillations in Hepatocytes." Journal of Theoretical Biology, vol. 503, 2020, p. 110390.
Cloete I, Bartlett PJ, Kirk V, et al. Dual mechanisms of Ca2+ oscillations in hepatocytes. J Theor Biol. 2020;503:110390.
Cloete, I., Bartlett, P. J., Kirk, V., Thomas, A. P., & Sneyd, J. (2020). Dual mechanisms of Ca2+ oscillations in hepatocytes. Journal of Theoretical Biology, 503, 110390. https://doi.org/10.1016/j.jtbi.2020.110390
Cloete I, et al. Dual Mechanisms of Ca2+ Oscillations in Hepatocytes. J Theor Biol. 2020 Oct 21;503:110390. PubMed PMID: 32628939.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual mechanisms of Ca2+ oscillations in hepatocytes. AU - Cloete,Ielyaas, AU - Bartlett,Paula J, AU - Kirk,Vivien, AU - Thomas,Andrew P, AU - Sneyd,James, Y1 - 2020/07/03/ PY - 2020/03/24/received PY - 2020/06/19/revised PY - 2020/06/24/accepted PY - 2020/7/7/pubmed PY - 2020/7/7/medline PY - 2020/7/7/entrez KW - KW - receptors KW - Models of calcium oscillations KW - Signal transduction SP - 110390 EP - 110390 JF - Journal of theoretical biology JO - J. Theor. Biol. VL - 503 N2 - Calcium (Ca2+) oscillations in hepatocytes control many critical cellular functions, including glucose metabolism and bile secretion. The mechanisms underlying repetitive Ca2+ oscillations and how these mechanisms regulate these oscillations is not fully understood. Recent experimental evidence has shown that both Ca2+ regulation of the inositol 1,4,5-trisphosphate (IP3) receptor and IP3 metabolism generate Ca2+ oscillations and co-exist in hepatocytes. To investigate the effects of these feedback mechanisms on the Ca2+ response, we construct a mathematical model of the Ca2+ signalling network in hepatocytes. The model accounts for the biphasic regulation of Ca2+ on the IP3 receptor (IP3R) and the positive feedback from Ca2+ on IP3 metabolism, via activation of phospholipase C (PLC) by agonist and Ca2+. Model simulations show that Ca2+ oscillations exist for both constant [IP3] and for [IP3] changing dynamically. We show, both experimentally and in the model, that as agonist concentration increases, Ca2+ oscillations transition between simple narrow-spike oscillations and complex broad-spike oscillations. The model predicts that narrow-spike oscillations persist when Ca2+ transport across the plasma membrane is blocked. This prediction has been experimentally validated. In contrast, broad-spike oscillations are terminated when plasma membrane transport is blocked. We conclude that multiple feedback mechanisms participate in regulating Ca2+ oscillations in hepatocytes. SN - 1095-8541 UR - https://www.unboundmedicine.com/medline/citation/32628939/Dual_mechanisms_of_Ca2+_oscillations_in_hepatocytes L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-5193(20)30245-9 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.