Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 429, Issue 1-2, Pages 103-111Publisher
SPRINGER
DOI: 10.1007/s11010-017-2939-7
Keywords
Sinus bradycardia; RNA interference; Acetylcholine-sensitive potassium channel; Kir3.1; Gene therapy
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Funding
- Science and Technology Research Project of Shenyang Municipality [1091174-1-00]
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The objective of this study was to explore whether the inhibition of potassium inwardly rectifying channel (Kir3.1) with short interfering RNA (siRNA) can improve bradycardia in an experimental sinus bradycardia rat model. 54 Sprague Dawley (SD) rats were randomly divided into three groups: experimental group, control group, and sham group. Sinus bradycardia model was established in SD rats through chemical ablation of sinoatrial (SA) node with 20% formaldehyde. Variations of Kir3.1 expression at mRNA and protein level were examined with qPCR and Western blotting. Electrocardiograms (ECG) of rats at 3 days and 1, 2, 3, and 4 weeks after chemical ablation and lentivirus injection were recorded and differences were compared among the three groups. The differences among multiple groups were analyzed by one-way analysis of variance (ANOVA). It was found through RTPCR and Western blot that the mRNA and protein levels of Kir3.1 at sinoatrial node areas were decreased by 42 +/- 7% and 31 +/- 7% in comparison with control group, respectively (P < 0.05 in both comparisons) after 4 weeks of chemical ablation/injection. Whole-cell patch clamp data showed that the lentiviral construct could significantly inhibit the potassium current of a muscarinic acetylcholine-sensitive K+ channel, I-KACh. ECG data showed that the heart rate of experimental group increased after 3 days of chemical ablation/injection and lasted for at least 4 weeks after the chemical ablation/injection (heart rate increased 15.4 +/- 3.8% in comparison with control group, P < 0.05). Inhibition of Kir3.1 could rescue sinus bradycardia induced by chemical ablation of SA node with 20% formaldehyde at least partly through inhibiting I-KACh channel.
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