Figure 8. Relative contribution of each K⁺ current to net repolarizing K⁺ current in HF.

Relative contributions and magnitudes of the major repolarizing K⁺ currents (I_Kr, I_Ks, I_K1) during AP are compared in different phases of the repolarization process in HF to those in age-matched control. (A) I_Kr, I_Ks and I_K1 traces in control and HF measured under AP-clamp at 2 Hz without using any Ca²⁺ buffer or β-AR agonist. Mean traces and SEM are shown. (B) When [Ca²⁺]_i cycling is preserved, upregulation of I_Kr and I_Ks compensates the decrease of I_K1 in HF during phase 3 of AP. (C) Stimulation of β-ARs using isoproterenol (ISO, 10 nM) significantly upregulates I_Ks, thus ISO reverses I_Kr/I_Ks dominant pattern of repolarization during phase 3 of AP. However, HF cells are hyporesponsive to ISO-induced stimulation (i.e. I_Ks increases in a smaller extent than in control) thus the net repolarizing current is largely reduced in HF compared to control. Reversal in I_Kr/I_Ks dominance in repolarization following ISO treatment also fail to happen in HF. (D) CaMKII inhibition using the specific inhibitory peptide AIP abolishes the increase in I_Ks, whereas it does not affect I_Kr and I_K1. (E) When [Ca²⁺]_i is buffered (BAPTA_i), the reduction in I_K1 without the upregulation of I_Kr and I_Ks results in a significant decrease in the net repolarizing current in HF. (F) Under β-adrenergic stimulation in BAPTA_i, HF cells show decrease in all three K⁺ currents compared to control. The contributions of these K⁺ currents to total net charge are shown in the insets. Columns and bars represent mean±SEM. Statistics and n numbers are shown in Figs. 3–6.