The peptide corresponding to the second extracellular loop ofangiotensin Ⅱ type 1 receptor (AT1R-ECⅡ)activating autoantibody (AT1-Ab), which was first detected in preeclampsia, can induce vascular smooth muscle cell (SMC) phenotypic switch.However, the underlying mechanisms are still unclear.Large conductance calciumactivated potassium channel (BKCa) is one of the important channels for maintaining the SMC differentiated phenotype.Therefore, the current study aimed to determine the direct effect ofAT1-Ab on BKCa channel activity in rat mesenteric artery SMC.AT1-Ab was obtained from rat models which were actively immunized with synthetic peptide corresponding to human AT1R-ECⅡ.The BKCa single-channel current was recorded in 140mmol/L symmetric K+ condition, and the conductance was 194±2.9 pS.Under the cell-attached patch recording mode, the activity of BKCa channel in SMC of rat mesenteric artery was significantly inhibited by 100 nM AT1-Ab in vitro, evidenced by decreased channel open probability, abbreviated average channel open time, and extended average close time.However, the vehicle group IgGs have no significant effect on activity of BKCa channel.As the same as angiotensin Ⅱ, the inhibition effects ofAT1-Ab on BKCa channel was significantly reversed when pretreated the cells with losartan (AT1 receptor blocker) but not with PD123319 (AT2 receptor blocker).All these data suggested that AT1-Ab can inhibit the activity of BKCa channel in vascular SMC through the activation of AT1 R, which may be one of the important mechanisms underlying the SMC phenotypic changes caused by AT1-Ab.