Fig. 1

THIK-1 regulates the electrical membrane properties in microglia in the human brain. A Top: anatomical localisation of human temporal lobe from which acute brain slices were prepared. Bottom: specimen images of morphologically identified microglia patch clamped in human (top) and murine (bottom) brain slices (scale bar, 50 µm) and after filling them with Alexa-488 via the patch solution (scale bar, 20 µm). B Membrane currents with capacitive and leak components in response to 10 mV hyperpolarizing voltage steps of human und murine microglia, from which electrical membrane properties were determined. C, D Comparison of input resistance (C), and resting membrane potential (D) of human and murine microglia. E Specimen current profiles in response to voltage steps from − 150 to + 60 mV of a human and murine microglia (left) and respective plot of voltage dependence for all cells per condition (right). F Effect of THIK-1 inhibitor, C100814, on the resting membrane potential of human microglia, illustrating the time course of changes of an individual cell (left) and the resulting mean depolarization (right). G Specimen recording showing C100814-induced changes in tonic THIK-1 current (left) and voltage dependence of respective C100814-inhibited current (right), revealing a reversal potential of ~ − 90 mV close to the predicted K⁺ equilibrium potential (inset, right). H Time course of changes in resting membrane potential by C100814 in murine microglia (left) and quantification of effects in comparison to mice lacking THIK-1 (THIK-1 KO) (right). Note the similar degree of depolarization obtained after pharmacological blockade and genetic deletion. I Example trace showing the lack of effect of C100814 on baseline current in microglia from THIK-1 KO mice (left) and quantification of effect relative to values before drug application (right). Data information: data indicate mean ± SEM. Dots on bars show number of cells. Data are from four individual patients, and four mice. P-values are from unpaired (C, D, H) and paired (F, H, I) Student’s t tests