The role of microglia membrane potential in chemotaxis

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<jats:title>Abstract</jats:title><jats:p>Microglia react to danger signals by rapid and targeted extension of cellular processes towards the source of the signal. This positive chemotactic response is accompanied by a hyperpolarization of the microglia membrane. Here, we show that optogenetic depolarization of microglia has little effect on baseline motility, but significantly slows down the chemotactic response. Reducing the extracellular Ca<jats:sup>2+</jats:sup> concentration mimics the effect of optogenetic depolarization. As the membrane potential sets the driving force for Ca<jats:sup>2+</jats:sup> entry, hyperpolarization is an integral part of rapid stimulus-response coupling in microglia. Compared to typical excitable cells such as neurons, the sign of the activating response is inverted in microglia, leading to inhibition by depolarizing channelrhodopsins.</jats:p>

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