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

Chih Chieh Yu, Christopher Corr, Changyu Shen, Richard Shelton, Mrinal Yadava, Isaac B. Rhea, Susan Straka, Michael C. Fishbein, Zhenhui Chen, Shien Fong Lin, John C. Lopshire, Peng Sheng Chen

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Background - The transmural distribution of apamin-sensitive small conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (SK) current (I<inf>KAS</inf>) 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<inf>KAS</inf> 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.

Original languageEnglish (US)
Pages (from-to)667-676
Number of pages10
JournalCirculation: Arrhythmia and Electrophysiology
Volume8
Issue number3
DOIs
StatePublished - Jun 4 2015

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Keywords

  • action potential
  • calcium
  • heart failure
  • ion channels
  • ventricular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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