L-type Ca2+ channels: a new player in the regulation of Ca2+ signaling, cell activation and cell survival in immune cells

Abstract

Ca(2+) is a highly versatile intracellular second messenger in many cell types, and regulates many complicated cellular processes, including cell activation, proliferation and apoptosis. Influx of Ca(2+) from the extracellular fluid is required for sustained elevation of the cytosolic Ca(2+) concentration and full activation of Ca(2+)-dependent processes. It is widely accepted that Ca(2+) release-activated Ca(2+) channels are the major routes of Ca(2+) influx in electrically non-excitable cells, including hematopoietic cells, whereas voltage-gated Ca(2+) channels such as L-type Ca(2+) channels (LTCCs) serve as the principal routes of Ca(2+) entry into electrically excitable cells such as neurons and myocytes. However, recent pharmacological and molecular genetic studies have revealed the existence of functional LTCCs and/or LTCC-like channels in a variety of immune cells including mast cells. In this article, we review recent advances in our understanding of Ca(2+) signaling in immune cells with a special interest in mast cells. We highlight roles for LTCCs in antigen receptor-mediated mast cell activation and survival.