Figure 3

Effects of reversing remodeling of individual ionic channels on the cytosolic calcium concentration ([Ca2+]i) and action potential (AP). (a) Characteristics of homozygous TBX5-knockout (Hom-Tbx5) atrial cells without each remodeled cellular component, i.e., INa, Ito, IKur, Jup, Jrel and IK1, respectively. Spontaneous depolarizations were suppressed in human atrial cells without the remodeled IK1. Action potential duration (APD90) was well restored when the remodeling of INa, IKur and Jup were individually reversed. Diastolic calcium was decreased in Hom-Tbx5 atrial cells without effects of the remodeled Jrel and Jup. (b–d) The diastolic calcium concentration (Cadiast), resting membrane potential (RMP) and APD90 for all cell variants were compared to those of Hom-Tbx5 atrial myocytes (red bar). Main components which contribute to AP abnormalities in Hom-Tbx5 atrial cells are marked with green rectangles. Biomarkers of the normal action potential are marked with stars.