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Small-conductance calcium-activated potassium current modulates the ventricular escape rhythm in normal rabbit hearts.
Wan, Juyi; Chen, Mu; Wang, Zhuo; Everett, Thomas H; Rubart-von der Lohe, Michael; Shen, Changyu; Qu, Zhilin; Weiss, James N; Boyden, Penelope A; Chen, Peng-Sheng.
Afiliación
  • Wan J; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiothoracic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, China.
  • Chen M; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • Wang Z; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Everett TH; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
  • Rubart-von der Lohe M; Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana.
  • Shen C; Richard and Susan Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
  • Qu Z; Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at the University of California, Los Angeles, California.
  • Weiss JN; Departments of Medicine (Cardiology) and Physiology, David Geffen School of Medicine at the University of California, Los Angeles, California.
  • Boyden PA; Department of Pharmacology, Columbia University, New York, New York.
  • Chen PS; Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: chenpp@iu.edu.
Heart Rhythm ; 16(4): 615-623, 2019 04.
Article en En | MEDLINE | ID: mdl-30445170
BACKGROUND: The apamin-sensitive small-conductance calcium-activated K (SK) current IKAS modulates automaticity of the sinus node. IKAS blockade by apamin causes sinus bradycardia. OBJECTIVE: The purpose of this study was to test the hypothesis that IKAS 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, IKAS 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apamina / Taquicardia Ventricular / Canales de Potasio de Pequeña Conductancia Activados por el Calcio / Bloqueo Atrioventricular Límite: Animals Idioma: En Revista: Heart Rhythm Año: 2019 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Apamina / Taquicardia Ventricular / Canales de Potasio de Pequeña Conductancia Activados por el Calcio / Bloqueo Atrioventricular Límite: Animals Idioma: En Revista: Heart Rhythm Año: 2019 Tipo del documento: Article País de afiliación: China