Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion

Significance ATP mediates interactions between cells in many tissues, but is particularly important for microglia, the brain’s immune cells, which constantly survey the brain to detect infection and regulate the brain’s wiring during development. It is controversial whether the ceaseless movement of microglia is driven by ATP release from brain cells. We show that an enzyme (apyrase) widely used to manipulate ATP levels is contaminated with K + ions which inhibit microglial surveillance, and that no ATP release is needed to drive microglial process movement. Thus, all conclusions about a role of ATP in signaling based on applying apyrase need reexamining, and brain immune surveillance is not regulated by ATP release.