Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells

Wei Chung Tsai, Yi Hsin Chan, Chia Hsiang Hsueh, Thomas Everett, Po Cheng Chang, Eue Keun Choi, Michael A. Olaopa, Shien-Fong Lin, Changyu Shen, Maria Aleksandra Kudela, Michael Rubart-von der Lohe, Zhenhui Chen, Pooja Jadiya, Dhanendra Tomar, Emily Luvison, Nicholas Anzalone, Vickas V. Patel, Peng-Sheng Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca2+ in melanocytes. Homozygous Dct knockout (Dct-/-) adult mice are vulnerable to atrial arrhythmias (AA). Objective: The purpose of this study was to determine whether apamin-sensitive small conductance Ca2+-activated K+ (SK) currents are upregulated in Dct-/- mice and contribute to AA. Methods: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct-/- (n = 9) and Dct+/- (n = 9) mice. Results: Apamin prolonged action potential duration (APD) by 18.8 ms (95% confidence interval [CI] 13.4-24.1 ms) in Dct-/- mice and by 11.5 ms (95% CI 5.4-17.6 ms) in Dct+/- mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95% CI 34-62 ms) for Dct-/- mice and 21 ms (95% CI 12-29 ms) for Dct+/- mice (P = .002) at baseline, and it was 35 ms (95% CI 21-49 ms) for Dct-/- mice and 22 ms (95% CI 11-32 ms) for Dct+/- mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95% CI 3.9-14.0 ms) in Dct-/- mice and by 1.5 ms (95% CI 0.7-2.3 ms) in Dct+/- mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct-/- mice. AA inducibility (89% vs 11%; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct-/- mice than in Dct+/- mice at baseline, but not different (22% vs 11%; P = 1.00) after apamin administration. Five of 8 (63%) induced atrial fibrillation episodes in Dct-/- mice had focal drivers. Conclusion: Apamin-sensitive SK current upregulation in Dct-/- mice plays an important role in the mechanism of AA.

Original languageEnglish (US)
JournalHeart Rhythm
DOIs
StateAccepted/In press - 2016

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Melanocytes
Cardiac Arrhythmias
Potassium
Calcium
Apamin
Confidence Intervals
dopachrome isomerase
Action Potentials
Heart Atria
Melanins

Keywords

  • Apamin
  • Atrial fibrillation
  • Melanocyte-like cells
  • Optical mapping
  • SK channels

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells. / Tsai, Wei Chung; Chan, Yi Hsin; Hsueh, Chia Hsiang; Everett, Thomas; Chang, Po Cheng; Choi, Eue Keun; Olaopa, Michael A.; Lin, Shien-Fong; Shen, Changyu; Kudela, Maria Aleksandra; Rubart-von der Lohe, Michael; Chen, Zhenhui; Jadiya, Pooja; Tomar, Dhanendra; Luvison, Emily; Anzalone, Nicholas; Patel, Vickas V.; Chen, Peng-Sheng.

In: Heart Rhythm, 2016.

Research output: Contribution to journalArticle

Tsai, Wei Chung ; Chan, Yi Hsin ; Hsueh, Chia Hsiang ; Everett, Thomas ; Chang, Po Cheng ; Choi, Eue Keun ; Olaopa, Michael A. ; Lin, Shien-Fong ; Shen, Changyu ; Kudela, Maria Aleksandra ; Rubart-von der Lohe, Michael ; Chen, Zhenhui ; Jadiya, Pooja ; Tomar, Dhanendra ; Luvison, Emily ; Anzalone, Nicholas ; Patel, Vickas V. ; Chen, Peng-Sheng. / Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells. In: Heart Rhythm. 2016.
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title = "Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells",
abstract = "Background: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca2+ in melanocytes. Homozygous Dct knockout (Dct-/-) adult mice are vulnerable to atrial arrhythmias (AA). Objective: The purpose of this study was to determine whether apamin-sensitive small conductance Ca2+-activated K+ (SK) currents are upregulated in Dct-/- mice and contribute to AA. Methods: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct-/- (n = 9) and Dct+/- (n = 9) mice. Results: Apamin prolonged action potential duration (APD) by 18.8 ms (95{\%} confidence interval [CI] 13.4-24.1 ms) in Dct-/- mice and by 11.5 ms (95{\%} CI 5.4-17.6 ms) in Dct+/- mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95{\%} CI 34-62 ms) for Dct-/- mice and 21 ms (95{\%} CI 12-29 ms) for Dct+/- mice (P = .002) at baseline, and it was 35 ms (95{\%} CI 21-49 ms) for Dct-/- mice and 22 ms (95{\%} CI 11-32 ms) for Dct+/- mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95{\%} CI 3.9-14.0 ms) in Dct-/- mice and by 1.5 ms (95{\%} CI 0.7-2.3 ms) in Dct+/- mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct-/- mice. AA inducibility (89{\%} vs 11{\%}; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct-/- mice than in Dct+/- mice at baseline, but not different (22{\%} vs 11{\%}; P = 1.00) after apamin administration. Five of 8 (63{\%}) induced atrial fibrillation episodes in Dct-/- mice had focal drivers. Conclusion: Apamin-sensitive SK current upregulation in Dct-/- mice plays an important role in the mechanism of AA.",
keywords = "Apamin, Atrial fibrillation, Melanocyte-like cells, Optical mapping, SK channels",
author = "Tsai, {Wei Chung} and Chan, {Yi Hsin} and Hsueh, {Chia Hsiang} and Thomas Everett and Chang, {Po Cheng} and Choi, {Eue Keun} and Olaopa, {Michael A.} and Shien-Fong Lin and Changyu Shen and Kudela, {Maria Aleksandra} and {Rubart-von der Lohe}, Michael and Zhenhui Chen and Pooja Jadiya and Dhanendra Tomar and Emily Luvison and Nicholas Anzalone and Patel, {Vickas V.} and Peng-Sheng Chen",
year = "2016",
doi = "10.1016/j.hrthm.2016.03.011",
language = "English (US)",
journal = "Heart Rhythm",
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TY - JOUR

T1 - Small conductance calcium-activated potassium current and the mechanism of atrial arrhythmia in mice with dysfunctional melanocyte-like cells

AU - Tsai, Wei Chung

AU - Chan, Yi Hsin

AU - Hsueh, Chia Hsiang

AU - Everett, Thomas

AU - Chang, Po Cheng

AU - Choi, Eue Keun

AU - Olaopa, Michael A.

AU - Lin, Shien-Fong

AU - Shen, Changyu

AU - Kudela, Maria Aleksandra

AU - Rubart-von der Lohe, Michael

AU - Chen, Zhenhui

AU - Jadiya, Pooja

AU - Tomar, Dhanendra

AU - Luvison, Emily

AU - Anzalone, Nicholas

AU - Patel, Vickas V.

AU - Chen, Peng-Sheng

PY - 2016

Y1 - 2016

N2 - Background: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca2+ in melanocytes. Homozygous Dct knockout (Dct-/-) adult mice are vulnerable to atrial arrhythmias (AA). Objective: The purpose of this study was to determine whether apamin-sensitive small conductance Ca2+-activated K+ (SK) currents are upregulated in Dct-/- mice and contribute to AA. Methods: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct-/- (n = 9) and Dct+/- (n = 9) mice. Results: Apamin prolonged action potential duration (APD) by 18.8 ms (95% confidence interval [CI] 13.4-24.1 ms) in Dct-/- mice and by 11.5 ms (95% CI 5.4-17.6 ms) in Dct+/- mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95% CI 34-62 ms) for Dct-/- mice and 21 ms (95% CI 12-29 ms) for Dct+/- mice (P = .002) at baseline, and it was 35 ms (95% CI 21-49 ms) for Dct-/- mice and 22 ms (95% CI 11-32 ms) for Dct+/- mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95% CI 3.9-14.0 ms) in Dct-/- mice and by 1.5 ms (95% CI 0.7-2.3 ms) in Dct+/- mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct-/- mice. AA inducibility (89% vs 11%; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct-/- mice than in Dct+/- mice at baseline, but not different (22% vs 11%; P = 1.00) after apamin administration. Five of 8 (63%) induced atrial fibrillation episodes in Dct-/- mice had focal drivers. Conclusion: Apamin-sensitive SK current upregulation in Dct-/- mice plays an important role in the mechanism of AA.

AB - Background: The melanin synthesis enzyme dopachrome tautomerase (Dct) regulates intracellular Ca2+ in melanocytes. Homozygous Dct knockout (Dct-/-) adult mice are vulnerable to atrial arrhythmias (AA). Objective: The purpose of this study was to determine whether apamin-sensitive small conductance Ca2+-activated K+ (SK) currents are upregulated in Dct-/- mice and contribute to AA. Methods: Optical mapping was used to study the membrane potential of the right atrium in Langendorff perfused Dct-/- (n = 9) and Dct+/- (n = 9) mice. Results: Apamin prolonged action potential duration (APD) by 18.8 ms (95% confidence interval [CI] 13.4-24.1 ms) in Dct-/- mice and by 11.5 ms (95% CI 5.4-17.6 ms) in Dct+/- mice at a pacing cycle length of 150 ms (P = .047). The pacing cycle length threshold to induce APD alternans was 48 ms (95% CI 34-62 ms) for Dct-/- mice and 21 ms (95% CI 12-29 ms) for Dct+/- mice (P = .002) at baseline, and it was 35 ms (95% CI 21-49 ms) for Dct-/- mice and 22 ms (95% CI 11-32 ms) for Dct+/- mice (P = .025) after apamin administration. Apamin prolonged post-burst pacing APD by 8.9 ms (95% CI 3.9-14.0 ms) in Dct-/- mice and by 1.5 ms (95% CI 0.7-2.3 ms) in Dct+/- mice (P = .005). Immunoblot and quantitative polymerase chain reaction analyses showed that protein and transcripts levels of SK1 and SK3 were increased in the right atrium of Dct-/- mice. AA inducibility (89% vs 11%; P = .003) and duration (281 seconds vs 66 seconds; P = .008) were greater in Dct-/- mice than in Dct+/- mice at baseline, but not different (22% vs 11%; P = 1.00) after apamin administration. Five of 8 (63%) induced atrial fibrillation episodes in Dct-/- mice had focal drivers. Conclusion: Apamin-sensitive SK current upregulation in Dct-/- mice plays an important role in the mechanism of AA.

KW - Apamin

KW - Atrial fibrillation

KW - Melanocyte-like cells

KW - Optical mapping

KW - SK channels

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DO - 10.1016/j.hrthm.2016.03.011

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