Journal
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
Volume 8, Issue 3, Pages 667-676Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCEP.114.002296
Keywords
action potential; calcium; heart failure; ion channels; ventricular remodeling
Categories
Funding
- National Institutes of Health [P01 HL78931, R01 HL71140, R41 HL124741]
- Medtronic-Zipes Endowment
- Indiana University Health-Indiana University School of Medicine Strategic Research Initiative
- Piansky Family Trust
Ask authors/readers for more resources
Background The transmural distribution of apamin-sensitive small conductance Ca2+-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available