Objective To study the effects of estrogens ( 17α-ethynylestradiol and 17β-estradiol ) on the ATP-sensitive potassium channel ( KATP ) activities in the enzymatically ( collagenase and protease ) isolated ICR mouse ventricular cardiomyocytes using inside-out and cell-attached patch clamp techniques .Methods In the inside-out patch configurations, the two estrogens reduced the K ATP channel activities in a dose-dependent manner at -60 mV holding potential ( HP) .Results The half-maximal inhibitory concentration ( IC50 ) of the 17α-esthynylestradiol and the 17β-estradiol were 0.3μmol/L and 0.1 nmol/L, respectively.However, these agents had no effects on the pinacidil-and DNP-induced KATP channel activities in the cell-attached patch configuration.However, the inhibitory effect of KATP channel activities by the 17-estrogens or the anti-estrogens in the excised inside-out patch configuration were abolished by 1 pmol/L PDBu.Conclusions The results of this study demonstrate that some estrogens decrease the K ATP channel activity acting on the inside of the isolated cardiomyocytes , and play a protective role to cardiomyocytes .