Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles

Background— The transmural distribution of apamin-sensitive small conductance Ca 2+ -activated K + (SK) current ( I KAS ) in failing human ventricles remains unclear. Methods and Results— We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nmol/L apamin administration in all wedges and after sequential administration of apamin, chromanol, and E4031 in 4 wedges. Apamin prolonged APD from 363 ms (95% confidence interval CI, 341–385) to 409 (95% CI, 385–434; P <0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s (95% CI, 30–42) to 32 cm/s (95% CI, 27–37; P =0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only 1 wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol, and E4031 were 9.1% (95% CI, 3.9–14.2), 17.3% (95% CI, 3.1–31.5), and 35.9% (95% CI, 15.7–56.1), respectively. Immunohistochemical staining of subtype 2 of SK protein showed increased expression in intercalated discs of myocytes. Conclusions— SK current is important in the transmural repolarization in failing human ventricles. The magnitude of I KAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant subtype 2 of SK protein in the intercalated discs of myocytes.