GPCR mediated control of calcium dynamics: A systems perspective

Vaibhav Dhyani; Suman Gare; Rishikesh Kumar Gupta; Sarpras Swain; K V Venkatesh; Lopamudra Giri

doi:10.1016/j.cellsig.2020.109717

GPCR mediated control of calcium dynamics: A systems perspective

Cell Signal. 2020 Oct:74:109717. doi: 10.1016/j.cellsig.2020.109717. Epub 2020 Jul 22.

Authors

Vaibhav Dhyani¹, Suman Gare¹, Rishikesh Kumar Gupta¹, Sarpras Swain¹, K V Venkatesh², Lopamudra Giri³

Affiliations

¹ Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Sangareddy, Telangana, India.
² Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India.
³ Department of Chemical Engineering, Indian Institute of Technology Hyderabad, Sangareddy, Telangana, India. Electronic address: giril@che.iith.ac.in.

Abstract

G-protein coupled receptor (GPCR) mediated calcium (Ca²⁺)-signaling transduction remains crucial in designing drugs for various complex diseases including neurodegeneration, chronic heart failure as well as respiratory diseases. Although there are several reviews detailing various aspects of Ca²⁺-signaling such as the role of IP₃ receptors and Ca²⁺-induced-Ca²⁺-release, none of them provide an integrated view of the mathematical descriptions of GPCR signal transduction and investigations on dose-response curves. This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Ca_c²⁺]-oscillations. The central theme of this paper is to present the biochemical pathways, as well as molecular mechanisms underlying the GPCR-mediated Ca²⁺-dynamics in order to facilitate a better understanding of how agonist concentration is encoded in Ca²⁺-signals for G_αq, G_αs, and G_αi/o signaling pathways. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases. The current paper presents the ODE formulation for various models along with the detailed schematics of signaling networks. To provide a systems perspective, we present the network motifs that can provide readers an insight into the complex and intriguing science of agonist-mediated Ca²⁺-dynamics. One of the features of this review is to pinpoint the interplay between positive and negative feedback loops that are involved in controlling intracellular [Ca_c²⁺]-oscillations. Furthermore, we review several examples of dose-response curves obtained from [Ca_c²⁺]-spiking for various GPCR pathways. This paper is expected to be useful for pharmacologists and computational biologists for designing clinical applications of GPCR targeting drugs through modulation of Ca²⁺-dynamics.

Keywords: Calcium dynamics; Cytosolic calcium; Dose-response; Feedback loops; GPCR; Mathematical models; Network motifs; Signal transduction.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Calcium / metabolism*
Calcium Signaling*
Humans
Receptors, G-Protein-Coupled / metabolism*

Substances

Receptors, G-Protein-Coupled
Calcium