Fig. 3: Endothelial Piezo1 shapes the functional hyperemic response.
From: Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow
a Left: Example FH response to whisker stimulation showing the increase in CBF shortly after the stimulus starts (upstroke) and the return to baseline at the end of the stimulation (downstroke). Right: A schematic showing that neuronal activity increases blood flow (FH), and the resulting change in forces activates cationic influx by opening Piezo1 channels, thus acting as a mechano-feedback system to attenuate FH. b Experimental setup illustrating impalement of a freshly isolated brain EC using a sharp microelectrode. ECs were obtained from a Pdgfrb-Cre-TdTomato mouse, where pericytes are TdTomato+. Scale bar = 10 µm. c Traces and summary data of Vm measurements showing the effect of Yoda1 (5 µM) on endothelial Vm (-Yoda1 [n = 16 ECs/5 mice]; +Yoda1 [n = 23 ECs/4 mice]). d, e Representative traces and scatter plots of functional hyperemia responses to whisker stimulations in Piezo1cx/cx;Cdh5-Cre+ (GOF) and Piezo1flox/flox;Cdh5-Cre+ (knockout) mice, and their respective controls (d: n = 6 GOF, 6 controls; e: n = 7 knockout, 5 controls). f Representative traces and plateau-followed-by-exponential fittings (dotted) to obtain time constant for downstroke (Tau), in a control mouse and a GOF mouse. Right: Scatter plot of downstroke Tau values in control (n = 5) and GOF (n = 6) mice. g Similar to f in knockout and control mice (n = 5 each). h Representative traces and plateau-followed-by-exponential fittings (dotted) to obtain upstroke Tau, in a control mouse and a GOF mouse. Right: Scatter plot of upstroke Tau values in control and GOF (n = 6 mice each). i Representative traces and averaged data of upstroke Tau in control and knockout mice (n = 5 mice each). FH responses were measured through a cranial window using laser Doppler flowmetry. Statistical tests were unpaired Student’s t test (two-sided, c), and Mann-Whitney test (one-sided in d–e, two-sided in f–i; *P < 0.05, **P < 0.01, ***P < 0.001). Error bars in c, d and e are SEM. Data in c, d, e are presented as mean values ± SEM, and data in f, g, h, i are presented as violin scatter plots. Source data are provided as a Source Data file.
