Dose-response effect of isoproterenol (ISO) on IKs, IKr and IK1 peak densities under AP-clamp at 2 Hz. Pipette solution contained 10 mM BAPTA. (A) IKs measured as HMR-sensitive current showed a robust accumulation following ISO application. IKS sensitivity (EC50) to ISO was unchanged in HF, whereas the response was significantly reduced in HF. (B) IKr was minimally affected by ISO treatment; however, neither the ISO-sensitivity nor the magnitude of the response were altered in HF. (C) IK1 peak density did not change following ISO application under buffered [Ca2+]i conditions and IK1 was uniformly decreased in HF. EC50 values, Hill coefficients and maximum responses were determined by fitting data to the Hill equation, indicated by solid lines. Symbols and bars represent mean±SEM. n refers to the number of cells measured in each group, and the cells in each group came from three to five individual animals. ANOVA with Bonferroni posttest, *p<0.05, **p<0.01, ***p<0.001.