Mind the translational gap: human microglia differ from mouse microglia in their regulation of K _v and K _ir 2.1 channels

Abstract K + channels are important for controlling membrane potential and regulating functional properties of microglia. Whereas the inward-rectifying K + (K ir ) channel 2.1 modulates proliferation, voltage-gated K + channels (K v ) are linked to inflammatory response in mouse microglia (mMG). These channels serve as possible drug targets but little is known regarding their activity in human microglia. We used patch-clamp recording to study membrane currents of primary human microglia (hMG) and human induced pluripotent stem cell-derived microglia-like cells (hiPSC-MGL) and compared them with mMG. Unlike mMG, hMG and hiPSC-MGL exhibited K ir 2.1 currents only after LPS+IFN-γ stimulation. Interestingly, K v currents were not observed in hMG or hiPSC-MGL under any condition. While mMG had a progressively ameboid morphology after stimulation, hMG showed few morphological changes and hiPSC-MGL increased ramification. Overall, the activity of K ir 2.1 and K v channels in hMG and hiPSC-MGL differs fundamentally from mMG. Our findings highlight differences between species and underscore the need for translational approaches.