Figure 6. Altered response of K⁺ currents to β-AR stimulation in HF.

I_Ks, I_Kr and I_K1 currents were recorded following 2 min pretreatment with beta-adrenergic receptor agonist isoproterenol (ISO, 10 nM). (A) I_Ks traces (mean±SEM) under canonical AP-clamp at 2 Hz measured with preserved [Ca²⁺]_i cycling (Physiol) and [Ca²⁺]_i buffering using 10 mM BAPTA in the pipette (BAPTA_i). (B) I_Kr traces (mean±SEM) under AP-clamp following ISO pretreatment in HF and age-matched control cells. (C) I_K1 traces (mean±SEM) under AP-clamp following ISO pretreatment in physiological solutions and in BAPTA_i. (D) Robust upregulation of I_Ks peak and net charge induced by ISO, which is reduced in BAPTA_i indicating a Ca²⁺-dependent pathway in mediating the response of β-AR stimulation on I_Ks besides the classical PKA-dependent phosphorylation. HF cells showed significantly reduced I_Ks accumulation upon ISO application both with and without [Ca²⁺]_i buffering. (E) I_Kr is slightly modulated by ISO both in control and HF. (F) I_K1 peak density is not influenced by ISO, but I_K1 net charge is slightly increased in HF due to altered rectification. Symbols and bars represent mean±SEM. n refers to 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.