Involvement of interaction between TRPM2 and IKCA1 in temperature-dependent movement and IL-1β production in mouse microglia.

Transient potential melastatin 2 (TRPM2) plays important roles in Ca2 + signaling in tissues and cells, and contributes to various cellular functions. The Ca2+ influx induced by TRPM2 may activate the intermediate conductance Ca2+-activated potassium channel (IKCA1/ KCa3.1/ SK4) and trigger K+ efflux. Here we demonstrate that a functional interaction between TRPM2 and IKCA1 contributes to cell volume changes in HEK293T cells and mouse primary microglia. Ca2+ entering cells through TRPM2 causes K+ efflux, followed by cell shrinkage upon water efflux. In addition, mouse microglia exhibited temperature-dependent movement in vitro that was modulated by the TRPM2-IKCA1 interaction within the physiological body temperature range. This interaction was also found to be involved in cytokine production in microglia. Understanding how the TRPM2-IKCA1 interaction in microglia can promote cell movement and cytokine production could be valuable for developing new strategies for treatments of diseases involving TRPM2.