Both heat-sensitive TRPV4 and cold-sensitive TRPM8 ion channels regulate microglial activity

Abstract

Microglia, the brain-resident macrophages, perform a myriad of functions directed towards development of neural circuits, and their maintenance. A plethora of ion channels aid in microglial activities that are critical for overall brain functioning. Notably, different functions of microglial cells are sensitive to minute temperature changes, as well as mechanical forces. Therefore, among all the players involved in the regulation of microglial functions, thermosensitive TRP ion channels are potentially important. In this study, we report the endogenous and functional presence of a heat-sensitive ion channel TRPV4 and a cold-sensitive ion channel TRPM8 in primary rat microglia and microglial cell line, N9. We demonstrate that pharmacological modulations of both these channels affect intracellular Ca²⁺-levels, cellular morphology, migration, and motility. Thus, TRPV4 and TRPM8 act as potential regulators of microglial activities. These findings may have broad implications in understanding neuro-glia interactions in neurodevelopmental and neurodegenerative pathologies with overall bio-medical applications.

Keywords: Ca(2+)-signaling; Microglia; Migration; Motility; TRPM8; TRPV4.