Calcium Signaling in Mast Cells: Focusing on L-Type Calcium Channels

Mast cells play central roles in adaptive and innate immunity. IgE-dependent stimulation of the high-affinity IgE receptor (Fc epsilon RI) results in rapid secretion of various proinflammatory chemical mediators and cytokines. All of the outputs depend to certain degrees on an increase in the intracellular Ca2+ concentration, and influx of Ca2+ from the extracellular space is often required for their full activation. There is strong evidence that FceRI stimulation induces two different modes of Ca2+ influx, store-operated Ca2+ entry (SOCE) and non-SOCE, which are activated in response to endoplasmic reticulum Ca2+ store depletion and independently of Ca2+ store depletion, respectively, in mast cells. Although Ca2+ release-activated Ca2+ channels are the major route of SOCE, recent evidence indicates that they are not the only Ca2+ channels activated by Ca2+ store depletion. The recent data suggest that L-type Ca2+ channels, which were thought to be a characteristic feature of excitable cells, exist in mast cells to mediate non-SOCE, which is critical for protecting mast cells against activation-induced mitochondrial cell death. In this chapter, we provide an overview of recent advances in our understanding of Ca2+ signaling in mast cells with a special attention to the emerging role for the L-type Ca2+ channels as a regulator of mast cell survival.