Emergence of broad cytosolic Ca2+ oscillations in the absence of CRAC channels: A model for CRAC-mediated negative feedback on PLC and Ca2+ oscillations through PKC.
J Theor Biol
; 581: 111740, 2024 03 21.
Article
em En
| MEDLINE
| ID: mdl-38253220
ABSTRACT
The role of Ca2+ release-activated Ca2+ (CRAC) channels mediated by ORAI isoforms in calcium signalling has been extensively investigated. It has been shown that the presence or absence of different isoforms has a significant effect on store-operated calcium entry (SOCE). Yoast et al. (2020) showed that, in addition to the reported narrow-spike oscillations (whereby cytosolic calcium decreases quickly after a sharp increase), ORAI1 knockout HEK293 cells were able to oscillate with broad-spike oscillations (whereby cytosolic calcium decreases in a prolonged manner after a sharp increase) when stimulated with a muscarinic agonist. This suggests that Ca2+ influx through ORAI-mediated CRAC channels negatively regulates the duration of Ca2+ oscillations. We hypothesise that, through the activation of protein kinase C (PKC), ORAI1 negatively regulates phospholipase C (PLC) activity to decrease inositol 1,4,5-trisphosphate (IP3) production and limit the duration of agonist-evoked Ca2+ oscillations. Based on this hypothesis, we construct a new mathematical model, which shows that the formation of broad-spike oscillations is highly dependent on the absence of ORAI1. Predictions of this model are consistent with the experimental results.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio Ativados pela Liberação de Cálcio
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Theor Biol
Ano de publicação:
2024
Tipo de documento:
Article