Microglia are the resident immune cells in the CNS. They survey their environment by extending and retracting their ramified processes, enabling them to react promptly to brain injury. ATP released from damaged cells activates microglia, inducing their processes to extend to the injured area. Here, we describe a novel microglial response elicited by mechanical changes in their microenvironment.

Microglial cells in rat and mouse hippocampal brain slices detect, in an extremely sensitive manner, sudden changes in extracellular flow (achieved by puff-applying Ringer's solution at < 5psi above the slice surface while avoiding any form of physical tissue distortion). Flow changes evoke a rise in [Ca²⁺]_i and an outward-rectifying K⁺ current both in resting and activated microglial cells, which hyperpolarises the cells from their resting membrane potential of -30mV to about -80mV. The same K⁺ current response is seen with the patch-clamped cell pulled more than 100mm out of the slice, with the aim of excluding indirect effects mediated by other cell types. The K⁺ current is inhibited by micromolar concentrations of quinidine, bupivacaine and Hg²⁺ but insensitive to 4-aminopyridine. The current was blocked by removing GTP/ATP from the pipette, or by buffering [Ca²⁺]_i with BAPTA. These data suggest that the puff-triggered response is mediated by a TWIK-related spinal cord potassium channel (TRESK, a two-pore domain potassium channel), downstream of a G protein mediated rise of [Ca²⁺]_i. This novel microglial flow sensor may enable microglia to detect brain concussion or changes in extracellular fluid flow caused by blood leaking from vessels.

(Supported by the Wellcome Trust).