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Updated: Apr 14, 2026
Isolation and Functional Characterization of Human Ventricular Cardiomyocytes from Fresh Surgical Samples
Published on: April 21, 2014
Small conductance calcium-activated potassium current is important in transmural repolarization of failing human
Chih-Chieh Yu1, Christopher Corr1, Changyu Shen1
1From the Department of Medicine, Division of Cardiology, Krannert Institute of Cardiology (C.-C.Y., C.C., R.S., M.Y., I.B.R., S.S., Z.C., S.-F.L., J.C.L., P.-S.C.) and Department of Biostatistics (C.S.), Indiana University School of Medicine, Indianapolis; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (C.-C.Y.); Fairbanks School of Public Health, School of Medicine, Indiana University, Indianapolis (C.S.); Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at University of California, Los Angeles (M.C.F.); Institute of Biomedical Engineering, National Chiao-Tung University, Hsin-Chu, Taiwan (S.-F.L.); and Department of Medicine, Roudebush Veterans Affairs Medical Center, Indianapolis, IN (J.C.L.).
Background:
The transmural distribution of apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) current (IKAS) 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 IKAS 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.
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