Work

Depression of CaV1.2 activation and expression in mast cells ameliorates allergic inflammation diseases

Year: 2024

Type: article

Abstract: Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca 2+ level, but the intake and effects of the intracellular Ca 2+ remain unclear. The Ca 2+ influx is controlled by members of Ca 2+ channels, among which calcium voltage-gated channel subunit alpha1 C (Ca V 1.2) is the most robust. This study aimed to reveal the role and underlying mechanism of MC Ca V 1.2 in allergic inflammation. We found that Ca V 1.2 participated in MC activation and allergic inflammation. Nimodipine (Nim), as a strong Ca V 1.2-specific antagonist, ameliorated allergic inflammation in mice. Further, Ca V 1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C (PKC), which calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzed. Overexpression or knockdown of MC Ca V 1.2 influenced MC activation. Importantly, Ca V 1.2 expression in MC had detrimental effects, while its deficiency ameliorated allergic pulmonary inflammation. Results provide novel insights into Ca V 1.2 function and a potential drug target for controlling allergic inflammation. • MC Ca V 1.2 deficiency or inhibition ameliorates degranulation and allergic inflammation. • The opening of MC Ca V 1.2 does not require depolarization of membrane potential. • MC Ca V 1.2 activation is triggered by CaMKII/PKC/Ser1928 phosphorylation.

Source: Journal of Pharmaceutical Analysis

DOI: 10.1016/j.jpha.2024.101149