Small-conductance calcium-activated potassium current modulates the ventricular escape rhythm in normal rabbit hearts

Juyi Wan, Mu Chen, Zhuo Wang, Thomas Everett, Michael Rubart-von der Lohe, Changyu Shen, Zhilin Qu, James N. Weiss, Penelope A. Boyden, Peng-Sheng Chen

Research output: Contribution to journalArticle

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Abstract

Background: The apamin-sensitive small-conductance calcium-activated K (SK) current I KAS modulates automaticity of the sinus node. I KAS blockade by apamin causes sinus bradycardia. Objective: The purpose of this study was to test the hypothesis that I KAS modulates ventricular automaticity. Methods: We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff-perfused rabbit ventricles with atrioventricular block (protocol 1) and on recorded transmembrane action potential of pseudotendons of superfused right ventricular endocardial preparations (protocol 2). Results: All preparations exhibited spontaneous ventricular escape rhythms. In protocol 1, apamin decreased the atrial rate from 186.2 ± 18.0 bpm to 163.8 ± 18.7 bpm (N = 6; P = .006) but accelerated the ventricular escape rate from 51.5 ± 10.7 bpm to 98.2 ± 25.4 bpm (P = .031). Three preparations exhibited bursts of nonsustained ventricular tachycardia and pauses, resulting in repeated burst termination pattern. In protocol 2, apamin increased the ventricular escape rate from 70.2 ± 13.1 bpm to 110.1 ± 2.2 bpm (P = .035). Spontaneous phase 4 depolarization was recorded from the pseudotendons in 6 of 10 preparations at baseline and in 3 in the presence of apamin. There were no changes of phase 4 slope (18.37 ± 3.55 mV/s vs 18.93 ± 3.26 mV/s, N = 3; P = .231, ), but the threshold of phase 0 activation (mV) reduced from –67.97 ± 1.53 to –75.26 ± 0.28 (P = .034). Addition of JTV-519, a ryanodine receptor 2 stabilizer, in 5 preparations reduced escape rate back to baseline. Conclusion: Contrary to its bradycardic effect in the sinus node, I KAS blockade by apamin accelerates ventricular automaticity and causes repeated nonsustained ventricular tachycardia in normal ventricles. ryanodine receptor 2 blockade reversed the apamin effects on ventricular automaticity.

Original languageEnglish (US)
JournalHeart Rhythm
DOIs
StatePublished - Jan 1 2019

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Apamin
Potassium
Rabbits
Calcium
Ryanodine Receptor Calcium Release Channel
Sinoatrial Node
Ventricular Tachycardia
Atrioventricular Block
Bradycardia
Membrane Potentials
Action Potentials

Keywords

  • Automaticity
  • Calcium clock
  • Idioventricular rhythm
  • Purkinje cells
  • Purkinje fibers
  • Ryanodine receptor
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Small-conductance calcium-activated potassium current modulates the ventricular escape rhythm in normal rabbit hearts. / Wan, Juyi; Chen, Mu; Wang, Zhuo; Everett, Thomas; Rubart-von der Lohe, Michael; Shen, Changyu; Qu, Zhilin; Weiss, James N.; Boyden, Penelope A.; Chen, Peng-Sheng.

In: Heart Rhythm, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: The apamin-sensitive small-conductance calcium-activated K (SK) current I KAS modulates automaticity of the sinus node. I KAS blockade by apamin causes sinus bradycardia. Objective: The purpose of this study was to test the hypothesis that I KAS modulates ventricular automaticity. Methods: We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff-perfused rabbit ventricles with atrioventricular block (protocol 1) and on recorded transmembrane action potential of pseudotendons of superfused right ventricular endocardial preparations (protocol 2). Results: All preparations exhibited spontaneous ventricular escape rhythms. In protocol 1, apamin decreased the atrial rate from 186.2 ± 18.0 bpm to 163.8 ± 18.7 bpm (N = 6; P = .006) but accelerated the ventricular escape rate from 51.5 ± 10.7 bpm to 98.2 ± 25.4 bpm (P = .031). Three preparations exhibited bursts of nonsustained ventricular tachycardia and pauses, resulting in repeated burst termination pattern. In protocol 2, apamin increased the ventricular escape rate from 70.2 ± 13.1 bpm to 110.1 ± 2.2 bpm (P = .035). Spontaneous phase 4 depolarization was recorded from the pseudotendons in 6 of 10 preparations at baseline and in 3 in the presence of apamin. There were no changes of phase 4 slope (18.37 ± 3.55 mV/s vs 18.93 ± 3.26 mV/s, N = 3; P = .231, ), but the threshold of phase 0 activation (mV) reduced from –67.97 ± 1.53 to –75.26 ± 0.28 (P = .034). Addition of JTV-519, a ryanodine receptor 2 stabilizer, in 5 preparations reduced escape rate back to baseline. Conclusion: Contrary to its bradycardic effect in the sinus node, I KAS blockade by apamin accelerates ventricular automaticity and causes repeated nonsustained ventricular tachycardia in normal ventricles. ryanodine receptor 2 blockade reversed the apamin effects on ventricular automaticity.",
keywords = "Automaticity, Calcium clock, Idioventricular rhythm, Purkinje cells, Purkinje fibers, Ryanodine receptor, Ventricular tachycardia",
author = "Juyi Wan and Mu Chen and Zhuo Wang and Thomas Everett and {Rubart-von der Lohe}, Michael and Changyu Shen and Zhilin Qu and Weiss, {James N.} and Boyden, {Penelope A.} and Peng-Sheng Chen",
year = "2019",
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journal = "Heart Rhythm",
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T1 - Small-conductance calcium-activated potassium current modulates the ventricular escape rhythm in normal rabbit hearts

AU - Wan, Juyi

AU - Chen, Mu

AU - Wang, Zhuo

AU - Everett, Thomas

AU - Rubart-von der Lohe, Michael

AU - Shen, Changyu

AU - Qu, Zhilin

AU - Weiss, James N.

AU - Boyden, Penelope A.

AU - Chen, Peng-Sheng

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The apamin-sensitive small-conductance calcium-activated K (SK) current I KAS modulates automaticity of the sinus node. I KAS blockade by apamin causes sinus bradycardia. Objective: The purpose of this study was to test the hypothesis that I KAS modulates ventricular automaticity. Methods: We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff-perfused rabbit ventricles with atrioventricular block (protocol 1) and on recorded transmembrane action potential of pseudotendons of superfused right ventricular endocardial preparations (protocol 2). Results: All preparations exhibited spontaneous ventricular escape rhythms. In protocol 1, apamin decreased the atrial rate from 186.2 ± 18.0 bpm to 163.8 ± 18.7 bpm (N = 6; P = .006) but accelerated the ventricular escape rate from 51.5 ± 10.7 bpm to 98.2 ± 25.4 bpm (P = .031). Three preparations exhibited bursts of nonsustained ventricular tachycardia and pauses, resulting in repeated burst termination pattern. In protocol 2, apamin increased the ventricular escape rate from 70.2 ± 13.1 bpm to 110.1 ± 2.2 bpm (P = .035). Spontaneous phase 4 depolarization was recorded from the pseudotendons in 6 of 10 preparations at baseline and in 3 in the presence of apamin. There were no changes of phase 4 slope (18.37 ± 3.55 mV/s vs 18.93 ± 3.26 mV/s, N = 3; P = .231, ), but the threshold of phase 0 activation (mV) reduced from –67.97 ± 1.53 to –75.26 ± 0.28 (P = .034). Addition of JTV-519, a ryanodine receptor 2 stabilizer, in 5 preparations reduced escape rate back to baseline. Conclusion: Contrary to its bradycardic effect in the sinus node, I KAS blockade by apamin accelerates ventricular automaticity and causes repeated nonsustained ventricular tachycardia in normal ventricles. ryanodine receptor 2 blockade reversed the apamin effects on ventricular automaticity.

AB - Background: The apamin-sensitive small-conductance calcium-activated K (SK) current I KAS modulates automaticity of the sinus node. I KAS blockade by apamin causes sinus bradycardia. Objective: The purpose of this study was to test the hypothesis that I KAS modulates ventricular automaticity. Methods: We tested the effects of apamin (100 nM) on ventricular escape rhythms in Langendorff-perfused rabbit ventricles with atrioventricular block (protocol 1) and on recorded transmembrane action potential of pseudotendons of superfused right ventricular endocardial preparations (protocol 2). Results: All preparations exhibited spontaneous ventricular escape rhythms. In protocol 1, apamin decreased the atrial rate from 186.2 ± 18.0 bpm to 163.8 ± 18.7 bpm (N = 6; P = .006) but accelerated the ventricular escape rate from 51.5 ± 10.7 bpm to 98.2 ± 25.4 bpm (P = .031). Three preparations exhibited bursts of nonsustained ventricular tachycardia and pauses, resulting in repeated burst termination pattern. In protocol 2, apamin increased the ventricular escape rate from 70.2 ± 13.1 bpm to 110.1 ± 2.2 bpm (P = .035). Spontaneous phase 4 depolarization was recorded from the pseudotendons in 6 of 10 preparations at baseline and in 3 in the presence of apamin. There were no changes of phase 4 slope (18.37 ± 3.55 mV/s vs 18.93 ± 3.26 mV/s, N = 3; P = .231, ), but the threshold of phase 0 activation (mV) reduced from –67.97 ± 1.53 to –75.26 ± 0.28 (P = .034). Addition of JTV-519, a ryanodine receptor 2 stabilizer, in 5 preparations reduced escape rate back to baseline. Conclusion: Contrary to its bradycardic effect in the sinus node, I KAS blockade by apamin accelerates ventricular automaticity and causes repeated nonsustained ventricular tachycardia in normal ventricles. ryanodine receptor 2 blockade reversed the apamin effects on ventricular automaticity.

KW - Automaticity

KW - Calcium clock

KW - Idioventricular rhythm

KW - Purkinje cells

KW - Purkinje fibers

KW - Ryanodine receptor

KW - Ventricular tachycardia

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