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

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

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Apamin
Potassium
Action Potentials
Calcium
Confidence Intervals
Muscle Cells
Allografts
Transplants
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles. / Yu, Chih Chieh; Corr, Christopher; Shen, Changyu; Shelton, Richard; Yadava, Mrinal; Rhea, Isaac B.; Straka, Susan; Fishbein, Michael C.; Chen, Zhenhui; Lin, Shien-Fong; Lopshire, John C.; Chen, Peng-Sheng.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 8, No. 3, 04.06.2015, p. 667-676.

Research output: Contribution to journalArticle

Yu, Chih Chieh ; Corr, Christopher ; Shen, Changyu ; Shelton, Richard ; Yadava, Mrinal ; Rhea, Isaac B. ; Straka, Susan ; Fishbein, Michael C. ; Chen, Zhenhui ; Lin, Shien-Fong ; Lopshire, John C. ; Chen, Peng-Sheng. / Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles. In: Circulation: Arrhythmia and Electrophysiology. 2015 ; Vol. 8, No. 3. pp. 667-676.
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abstract = "Background - The transmural distribution of apamin-sensitive small conductance Ca2+-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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T1 - Small Conductance Calcium-Activated Potassium Current Is Important in Transmural Repolarization of Failing Human Ventricles

AU - Yu, Chih Chieh

AU - Corr, Christopher

AU - Shen, Changyu

AU - Shelton, Richard

AU - Yadava, Mrinal

AU - Rhea, Isaac B.

AU - Straka, Susan

AU - Fishbein, Michael C.

AU - Chen, Zhenhui

AU - Lin, Shien-Fong

AU - Lopshire, John C.

AU - Chen, Peng-Sheng

PY - 2015/6/4

Y1 - 2015/6/4

N2 - Background - The transmural distribution of apamin-sensitive small conductance Ca2+-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.

AB - Background - The transmural distribution of apamin-sensitive small conductance Ca2+-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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KW - calcium

KW - heart failure

KW - ion channels

KW - ventricular remodeling

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