Impairment of survival signaling and efferocytosis in TRPC3-deficient macrophages

We have recently shown that in macrophages proper operation of the survival pathways phosphatidylinositol-3-kinase (PI3K)/AKT and nuclear factor kappa B (NFkB) has an obligatory requirement for constitutive, non-regulated Ca²⁺ influx. In the present work we examined if Transient Receptor Potential Canonical 3 (TRPC3), a member of the TRPC family of Ca²⁺-permeable cation channels, contributes to the constitutive Ca²⁺ influx that supports macrophage survival. We used bone marrow-derived macrophages obtained from TRPC3^−/− mice to determine the activation status of survival signaling pathways, apoptosis and their efferocytic properties. Treatment of TRPC3^+/+ macrophages with the pro-apoptotic cytokine TNFα induced time-dependent phosphorylation of IκBα, AKT and BAD, and this was drastically reduced in TRPC3^−/− macrophages. Compared to TRPC3^+/+ cells TRPC3^−/− macrophages exhibited reduced constitutive cation influx, increased apoptosis and impaired efferocytosis. The present findings suggest that macrophage TRPC3, presumably through its constitutive function, contributes to survival signaling and efferocytic properties.