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

Abstract：

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.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Wan J,Chen M,Wang Z,Everett TH 4th,Rubart-von der Lohe M,Shen C,Qu Z,Weiss JN,Boyden PA,Chen PS

doi

10.1016/j.hrthm.2018.10.033

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

615-623

issue

4

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(18)31119-6

journal_volume

16

pub_type

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