GPCR mediated control of calcium dynamics: A systems perspective.

This article is the first study in reviewing the network structures underlying GPCR signal transduction that control downstream [Cac2+]-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 by Ca2+-signaling. Moreover, we present the GPCR targeting drugs that are relevant for treating cardiac, respiratory, and neuro-diseases along with agonist concentration encoding of Ca2+-response corresponding to Gαq, Gαs, and Gαi/o signaling. 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 [Cac2+]-oscillations. Furthermore, we review several examples of dose-response curves obtained from [Cac2+]-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. PMID: 32711109 [PubMed - as supplied by publisher]
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research