Depression of Ca1.2 activation and expression in mast cells ameliorates allergic inflammation diseases.

Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca level, but the intake and effects of the intracellular Ca remain unclear. The Ca influx is controlled by members of Ca channels, among which calcium voltage-gated channel subunit alpha1 C (Ca1.2) is the most robust. This study aimed to reveal the role and underlying mechanism of MC Ca1.2 in allergic inflammation. We found that Ca1.2 participated in MC activation and allergic inflammation. Nimodipine (Nim), as a strong Ca1.2-specific antagonist, ameliorated allergic inflammation in mice. Further, Ca1.2 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 Ca1.2 influenced MC activation. Importantly, Ca1.2 expression in MC had detrimental effects, while its deficiency ameliorated allergic pulmonary inflammation. Results provide novel insights into Ca1.2 function and a potential drug target for controlling allergic inflammation.