Proarrhythmic effect of blocking the small conductance calcium activated potassium channel in isolated canine left atrium

Chia Hsiang Hsueh, Po Cheng Chang, Yu Cheng Hsieh, Thomas Reher, Peng-Sheng Chen, Shien-Fong Lin

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

BACKGROUND Small conductance calcium activated potassium (SKCa) channels are voltage insensitive and are activated by intracellular calcium. Genome-wide association studies revealed that a variant of SKCa is associated with lone atrial fibrillation in humans. Roles of SKCa in atrial arrhythmias remain unclear. OBJECTIVE To determine roles of SK Ca in atrial arrhythmias. METHODS Optical mapping using the isolated canine left atrium was performed. The optical action potential duration (APD) and induction of arrhythmia were evaluated before and after the addition of specific SKCa blockers-apamin or UCL-1684. RESULTS SKCa blockade significantly increased APD80 (188 ± 19 ms vs 147 ± 11 ms; P < .001). The pacing cycle length thresholds to induce 2:2 alternans, and wave breaks were prolonged by SKCa blockade. Increased APD heterogeneity was observed after the SKCa blockade, as measured by the difference between the maximum and the minimum APD (39 ± 4 ms vs 26 ± 5 ms; P < .05), by standard deviation (12.43 ± 2.36 ms vs 7.49 ± 1.47 ms; P < .001), or by coefficient of variation (6.68% ± 0.97% vs 4.90% ± 0.84%; P o .05). No arrhythmia was induced at baseline by an S1-S2 protocol. After SKCa blockade, 4 of 6 atria developed arrhythmia. CONCLUSIONS SKCa blockade promotes arrhythmia and prolongs the pacing cycle length threshold of 2:2 alternans and wave breaks in the canine left atrium. The proarrhythmic effect could be attributed to increased APD heterogeneity in the canine left atrium. This study provides supportive evidence of genome-wide association studies showing association of KCNN3 and lone atrial fibrillation.

Original languageEnglish
Pages (from-to)891-898
Number of pages8
JournalHeart Rhythm
Volume10
Issue number6
DOIs
StatePublished - Jun 2013

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Small-Conductance Calcium-Activated Potassium Channels
Heart Atria
Canidae
Cardiac Arrhythmias
Action Potentials
Genome-Wide Association Study
Atrial Fibrillation
Apamin
Calcium

Keywords

  • Action potential duration
  • Atrial arrhythmia
  • Optical mapping
  • Repolarization
  • SK

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Proarrhythmic effect of blocking the small conductance calcium activated potassium channel in isolated canine left atrium. / Hsueh, Chia Hsiang; Chang, Po Cheng; Hsieh, Yu Cheng; Reher, Thomas; Chen, Peng-Sheng; Lin, Shien-Fong.

In: Heart Rhythm, Vol. 10, No. 6, 06.2013, p. 891-898.

Research output: Contribution to journalArticle

Hsueh, Chia Hsiang ; Chang, Po Cheng ; Hsieh, Yu Cheng ; Reher, Thomas ; Chen, Peng-Sheng ; Lin, Shien-Fong. / Proarrhythmic effect of blocking the small conductance calcium activated potassium channel in isolated canine left atrium. In: Heart Rhythm. 2013 ; Vol. 10, No. 6. pp. 891-898.
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abstract = "BACKGROUND Small conductance calcium activated potassium (SKCa) channels are voltage insensitive and are activated by intracellular calcium. Genome-wide association studies revealed that a variant of SKCa is associated with lone atrial fibrillation in humans. Roles of SKCa in atrial arrhythmias remain unclear. OBJECTIVE To determine roles of SK Ca in atrial arrhythmias. METHODS Optical mapping using the isolated canine left atrium was performed. The optical action potential duration (APD) and induction of arrhythmia were evaluated before and after the addition of specific SKCa blockers-apamin or UCL-1684. RESULTS SKCa blockade significantly increased APD80 (188 ± 19 ms vs 147 ± 11 ms; P < .001). The pacing cycle length thresholds to induce 2:2 alternans, and wave breaks were prolonged by SKCa blockade. Increased APD heterogeneity was observed after the SKCa blockade, as measured by the difference between the maximum and the minimum APD (39 ± 4 ms vs 26 ± 5 ms; P < .05), by standard deviation (12.43 ± 2.36 ms vs 7.49 ± 1.47 ms; P < .001), or by coefficient of variation (6.68{\%} ± 0.97{\%} vs 4.90{\%} ± 0.84{\%}; P o .05). No arrhythmia was induced at baseline by an S1-S2 protocol. After SKCa blockade, 4 of 6 atria developed arrhythmia. CONCLUSIONS SKCa blockade promotes arrhythmia and prolongs the pacing cycle length threshold of 2:2 alternans and wave breaks in the canine left atrium. The proarrhythmic effect could be attributed to increased APD heterogeneity in the canine left atrium. This study provides supportive evidence of genome-wide association studies showing association of KCNN3 and lone atrial fibrillation.",
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AU - Chen, Peng-Sheng

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N2 - BACKGROUND Small conductance calcium activated potassium (SKCa) channels are voltage insensitive and are activated by intracellular calcium. Genome-wide association studies revealed that a variant of SKCa is associated with lone atrial fibrillation in humans. Roles of SKCa in atrial arrhythmias remain unclear. OBJECTIVE To determine roles of SK Ca in atrial arrhythmias. METHODS Optical mapping using the isolated canine left atrium was performed. The optical action potential duration (APD) and induction of arrhythmia were evaluated before and after the addition of specific SKCa blockers-apamin or UCL-1684. RESULTS SKCa blockade significantly increased APD80 (188 ± 19 ms vs 147 ± 11 ms; P < .001). The pacing cycle length thresholds to induce 2:2 alternans, and wave breaks were prolonged by SKCa blockade. Increased APD heterogeneity was observed after the SKCa blockade, as measured by the difference between the maximum and the minimum APD (39 ± 4 ms vs 26 ± 5 ms; P < .05), by standard deviation (12.43 ± 2.36 ms vs 7.49 ± 1.47 ms; P < .001), or by coefficient of variation (6.68% ± 0.97% vs 4.90% ± 0.84%; P o .05). No arrhythmia was induced at baseline by an S1-S2 protocol. After SKCa blockade, 4 of 6 atria developed arrhythmia. CONCLUSIONS SKCa blockade promotes arrhythmia and prolongs the pacing cycle length threshold of 2:2 alternans and wave breaks in the canine left atrium. The proarrhythmic effect could be attributed to increased APD heterogeneity in the canine left atrium. This study provides supportive evidence of genome-wide association studies showing association of KCNN3 and lone atrial fibrillation.

AB - BACKGROUND Small conductance calcium activated potassium (SKCa) channels are voltage insensitive and are activated by intracellular calcium. Genome-wide association studies revealed that a variant of SKCa is associated with lone atrial fibrillation in humans. Roles of SKCa in atrial arrhythmias remain unclear. OBJECTIVE To determine roles of SK Ca in atrial arrhythmias. METHODS Optical mapping using the isolated canine left atrium was performed. The optical action potential duration (APD) and induction of arrhythmia were evaluated before and after the addition of specific SKCa blockers-apamin or UCL-1684. RESULTS SKCa blockade significantly increased APD80 (188 ± 19 ms vs 147 ± 11 ms; P < .001). The pacing cycle length thresholds to induce 2:2 alternans, and wave breaks were prolonged by SKCa blockade. Increased APD heterogeneity was observed after the SKCa blockade, as measured by the difference between the maximum and the minimum APD (39 ± 4 ms vs 26 ± 5 ms; P < .05), by standard deviation (12.43 ± 2.36 ms vs 7.49 ± 1.47 ms; P < .001), or by coefficient of variation (6.68% ± 0.97% vs 4.90% ± 0.84%; P o .05). No arrhythmia was induced at baseline by an S1-S2 protocol. After SKCa blockade, 4 of 6 atria developed arrhythmia. CONCLUSIONS SKCa blockade promotes arrhythmia and prolongs the pacing cycle length threshold of 2:2 alternans and wave breaks in the canine left atrium. The proarrhythmic effect could be attributed to increased APD heterogeneity in the canine left atrium. This study provides supportive evidence of genome-wide association studies showing association of KCNN3 and lone atrial fibrillation.

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