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Effect of SK channel blockade on the cardiac arrhythmias in rats
Author(s) -
Gui Le,
Zhu JiHua,
Gu MingJun,
Chen QingHui
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1098.7
Subject(s) - ventricular fibrillation , blockade , effective refractory period , medicine , refractory period , cardiology , stimulation , electrophysiology , anesthesia , qt interval , sudden cardiac death , receptor
Ventricular fibrillation (VF) is the lethal event in sudden cardiac death. It has been reported that inhibition of Small‐Conductance Ca 2+ ‐Activated K + (SK) channels with UCL1684 terminates and protects against atrial fibrillation. The current study sought to determine the effect of UCL1684 on cardiac VF. In vivo epicardial electrophysiology recording was used to evaluate cardiac conduction and ventricular programmed stimulation was used to evaluate VF threshold in anesthetized rats. VF in 5 rats was induced by S1S1 stimulation among 5 animals tested in control group (100%), but, VF was induced in only 1 rat among 6 animals (17%) tested in UCL1684 pre‐treated group (0.1 mg/kg i.p.). The VF threshold among the control group averaged 6±4.2 mA which was dramatically lower than that in UCL1684 pre‐treated rat (>28 mA). In control group, the vulnerable period of cardiac cycle averaged 16.7±7.6 ms which was dramatically longer than that in UCL1684 pre‐treated rat (<5 ms). Ventricular effective refractory period and QT interval were similar between control and UCL1684 pre‐treated rats. These data indicate that SK channel blockade with UCL1684 may be a novel approach to preventing and treating ventricular arrhythmias. Blockade of SK channel protects against VF evoked by S1S1 stimulation and increases the VF threshold, but, the mechanism remains to be elucidated. Support: NNS30971223 (JHZ) and SDG2640130 (QHC).