Figure 4
Role of the TBX5-PITX2 regulatory loop in spontaneous depolarization generation. (a) Cytosolic calcium concentration ([Ca2+]i) and action potential (AP) characteristics in homozygous TBX5-knockout (Hom-Tbx5), heterozygous TBX5-knockout (Het-Tbx5), homozygous PITX2-knockout (Hom-Pitx2), heterozygous PITX2-knockout (Het-Pitx2) and heterozygous knockout of both PITX2 and TBX5 (Het-Pitx2-Tbx5) atrial cells. TBX5 insufficiency (e.g., Hom-Tbx5) led to AP prolongation and diastolic calcium elevation, whereas PITX2 insufficiency (e.g., Hom-Pitx2) caused AP abbreviation and a decrease in diastolic calcium. AP abnormalities induced by TBX5 haploinsufficiency were rescued by PITX2 haploinsufficiency. (b–d) The diastolic calcium concentration (Cadiast), resting membrane potential (RMP) and action potential duration (APD90) for all cell variants were compared to control atrial myocytes (black bar).
