Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes

Lanqing YANG; Na WU; Penghui CHEN; Zhiquan YUAN; Chengying LI; Long WU; Li ZHONG; Yafei LI

doi:10.16016/j.2097-0927.202306024

您当前的位置：

首页 >

文章列表页 >

Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes

Basic Medicine | 更新时间：2026-01-09

- Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes
- Journal of Army Medical University Vol. 46, Issue 2, Pages: 100-109(2024)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)：军事预防医学系军队流行病学教研室
  2.400038 重庆，陆军军医大学(第三军医大学)：基础医学院神经生物学教研室
  3.401120 重庆，重庆医科大学附属第三医院心血管疾病中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(82073649)
- DOI：10.16016/j.2097-0927.202306024
  CLC： R322.11;R329.25;R394.3
- Received：06 June 2023，
  
  Revised：2023-07-31，
  
  Published：30 January 2024
- 稿件说明：
移动端阅览
Lanqing YANG, Na WU, Penghui CHEN, et al. Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes[J]. Journal of Army Medical University, 2024, 46(2): 100-109.
DOI：

Lanqing YANG, Na WU, Penghui CHEN, et al. Circular RNA mmu_circ_0005019 regulates small conductance calcium-activated potassium current and action potential duration in mouse cardiomyocytes[J]. Journal of Army Medical University, 2024, 46(2): 100-109. DOI： 10.16016/j.2097-0927.202306024.

摘要

目的

探索环状RNA mmu_circ_0005019调控小电导钙激活钾(small-conductance calcium-activated potassium，SK)通道蛋白亚基SK3编码基因Kcnn3的表达，以及对小电导钙激活钾通道电流(I

)和动作电位时程(action potential duration，APD)的影响。

方法

在小鼠HL-1细胞中分别构建mmu_circ_0005019过表达和干扰模型，分为过表达组(

=3)、空质粒组(

=3)、干扰1组(

=3)、干扰2组(

=3)、对照组(

=3)，通过RT-qPCR、Western blot分析mmu_circ_0005019调节Kcnn3表达的分子机制，应用膜片钳技术电流钳模式记录全细胞的I

，并用电压钳模式记录APD。

结果

成功构建了环状RNA mmu_circ_0005019过表达和干扰的HL-1细胞模型。过表达组的Kcnn3基因表达与空质粒组相比明显上调(

0.05)；干扰1组和干扰2组的Kcnn3基因表达与对照组相比均明显下调(

0.05)。电生理发现过表达mmu_circ_0005019增加了HL-1细胞I

电流密度，APD显著缩短；相反，干扰mmu_circ_0005019减少了I

电流密度，APD显著延长。

结论

mmu_circ_0005019可以上调小鼠HL-1细胞Kcnn3的表达水平，从而改变I

和APD，提示环状RNA mmu_circ_0005019可能在房颤发生中起到促进作用。

Abstract

Objective

To investigate the effect of mmu_circ_0005019 on regulating Kcnn3 expression

small conductance calcium-activated potassium current (I

) which is generated by the small conductance calcium-ac

tivated potassium (SK) channel that is partly coded by Kcnn3

and action potential duration (APD).

Methods

We transfected pcDNA3.1-mmu_circ_0005019 expressing vectors and 2 independent small interfering RNAs into HL-1 cells to establish gain- and loss-of-expression cell models

respectively. The transfected cells were divided into overexpression group(

=3)

empty vector group(

=3)

interference 1 group(

=3)

interference 2 group(

=3)

and blank control group(

=3). RT-qPCR and Western blotting were used to determine the expression of Kcnn3. Whole-cell patch clamp technology was performed to record the I

and APD. The effects of mmu_circ_0005019 on Kcnn3 expression

and APD were observed.

Results

Gain- and loss-of-expression cell models were established successfully. The expression of Kcnn3 and I

current density significantly increased

and the APD was shortened in overexpression group compared with empty vector group(

0.05). The expression of Kcnn3 and I

current density were significantly decreased

and the APD was prolonged in interference groups compared with blank control group(

0.05).

Conclusion

Mmu_circ_0005019 promotes the expression of Kcnn3 and its coding channel protein

which regulates I

and APD in mouse cardiomyocytes

and may play a promoting role in the occurrence of atrial fibrillation.

关键词

Keywords

references

BRUNDEL B J J M, AI X, HILLS M T, et al . Atrial fibrillation[J ] . Nat Rev Dis Primers, 2022, 8(1): 1-23. DOI: 10.1038/s41572-022-00347-9.

SCHNABEL R B, YIN X Y, GONA P, et al . 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study[J ] . Lancet, 2015, 386(9989): 154-162. DOI: 10.1016/S0140-6736(14)61774-8.

MEMCZAK S, JENS M, ELEFSINIOTI A, et al . Circular RNAs are a large class of animal RNAs with regulatory potency[J ] . Nature, 2013, 495(7441): 333-338. DOI: 10.1038/nature11928.

LIU C X, CHEN LL. Circular RNAs: characterization, cellular roles, and applications[J]. Cell, 2022, 185(12): 2016-2034. DOI: 10.1016/j.cell.2022.04.021.

LU D C, THUM T. RNA-based diagnostic and therapeutic strategies for cardiovascular disease[J]. Nat Rev Cardiol, 2019, 16(11): 661-674. DOI: 10.1038/s41569-019-0218-x.

WU N, LI J, CHEN X H, et al . Identification of long non-coding RNA and circular RNA expression profiles in atrial fibrillation[J ] . Heart Lung Circ, 2020, 29(7): e157-e167. DOI: 10.1016/j.hlc.2019.10.018.

CHEN Y C, VOSKOBOINIK A, GERCHE A, et al . Prevention of pathological atrial remodeling and atrial fibrillation: JACC state-of-the-art review[J ] . J Am Coll Cardiol, 2021, 77(22): 2846-2864. DOI: 10.1016/j.jacc.2021.04.012.

NAGY N, SZUTS V, HORVÁTH Z, et al . Does small-conductance calcium-activated potassium channel contribute to cardiac repolarization?[J ] . J Mol Cell Cardiol, 2009, 47(5): 656-663. DOI: 10.1016/j.yjmcc.2009.07.019.

IWASAKI Y K, NISHIDA K, KATO T, et al . Atrial fibrillation pathophysiology: implications for management[J ] . Circulation, 2011, 124(20): 2264-2274. DOI: 10.1161/CIRCULATIONAHA.111.019893.

DINESS J G, BENTZEN B H, SØRENSEN U S, et al . Role of calcium-activated potassium channels in atrial fibrillation pathophysiology and therapy[J ] . J Cardiovasc Pharmacol, 2015, 66(5): 441-448. DOI: 10.1097/FJC.0000000000000249.

LI M L, LI T, LEI M, et al . Increased small conductance calcium-activated potassium channel (SK2 channel) current in atrial myocytes of patients with persistent atrial fibrillation[J ] . Chin J Cardiol, 2011, 39(2): 147-151.

ZHANG X D, TIMOFEYEV V, LI N, et al . Critical roles of a small conductance Ca 2+ -activated K + channel (SK3) in the repolarization process of atrial myocytes[J ] . Cardiovasc Res, 2014, 101(2): 317-325. DOI: 10.1093/cvr/cvt262..

LI H, XU J D, FANG X H, et al . Circular RNA circRNA_000203 aggravates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p binding to Gata4[J ] . Cardiovasc Res, 2020, 116(7): 1323-1334. DOI: 10.1093/cvr/cvz215.

XU J D, DU W W, WU N, et al . The circular RNA circNlgnmediates doxorubicin-inducedcardiac remodeling and fibrosis[J ] . Mol Ther Nucleic Acids, 2022, 28: 175-189. DOI: 10.1016/j.omtn.2022.03.007.

JIN X, XU Y Y, GUO M, et al . hsa_circNFXL1_009 modulates apoptosis, proliferation, migration, and potassium channel activation in pulmonary hypertension[J ] . Mol Ther Nucleic Acids, 2021, 23: 1007-1019. DOI: 10.1016/j.omtn.2020.09.029.

ZHAO M N, WANG R J, YANG K M, et al . Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis[J ] . Acta Pharm Sin B, 2023, 13(3): 916-941. DOI: 10.1016/j.apsb.2022.10.019.

WANG L J, XU G E, SPANOS M, et al . Circular RNAs in cardiovascular diseases: regulation and therapeutic applications[J ] . Research (Wash D C), 2023, 6: 0038. DOI: 10.34133/research.0038.

GHAFOURI-FARD S, SHIRVANI-FARSANI Z, HUSSEN B M, et al . The key roles of non-coding RNAs in the pathophysiology of hypertension[J ] . Eur J Pharmacol, 2022, 931: 175220. DOI: 10.1016/j.ejphar.2022.175220.

WU N, LI C Y, XU B, et al . Circular RNA mmu_circ_0005019 inhibits fibrosis of cardiac fibroblasts and reverses electrical remodeling of cardiomyocytes[J ] . BMC Cardiovascular Disorders, 2021, 21(1): 308. DOI:10.1186/s12872-021-02128-w.

QI X Y, DINESS J G, BRUNDEL B J, et al . Role of small-conductance calcium-activated potassium channels in atrial electrophysiology and fibrillation in the dog[J ] . Circulation, 2014, 129(4): 430-440. DOI: 10.1161/CIRCULATIO NAHA.113.003019.

LIU T, LI T, XU D D, et al . Small-conductance calcium-activated potassium channels in the heart: expression, regulation and pathological implications[J ] . Philos Trans R Soc Lond B Biol Sci, 2023, 378(1879): 20220171. DOI: 10.1098/rstb.2022.0171.

MAHIDA S, MILLS R W, TUCKER N R, et al . Overexpression of KCNN 3 results in sudden cardiac death[J ] . Cardiovasc Res, 2014, 101(2): 326-334. DOI: 10.1093/cvr/cvt269..

HEIJMAN J, HOHNLOSER S H, CAMM A J. Antiarrhythmic drugs for atrial fibrillation: lessons from the past and opportunities for thefuture[J]. EP Eur, 2021, 23(Supplement_2): ⅱ14-ⅱ22. DOI: 10.1093/europace/euaa426.

SKIBSBYE L, POULET C, DINESS J G, et al . Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria[J ] . Cardiovasc Res, 2014, 103(1): 156-167. DOI: 10.1093/cvr/cvu121.

DINESS J G, KIRCHHOFF J E, SPEERSCHNEIDER T, et al . The KCa 2 channel inhibitor AP30663 selectively increases atrial refractoriness, converts vernakalant-resistant atrial fibrillation and prevents its reinduction in conscious pigs[J ] . Front Pharmacol, 2020, 11: 159. DOI: 10.3389/fphar.2020.00159..

GUPTA A, KAFETZIS K N, TAGALAKIS A D, et al . RNA therapeutics in ophthalmology—translation to clinical trials[J ] . Exp Eye Res, 2021, 205: 108482. DOI: 10.1016/j.exer.2021.108482.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Circ-gabra5 exacerbates cognitive impairment in Alzheimer’s disease mice by regulating AKT through miR-455-3p

Molecular mechanism of circ-Tns3/miR-671-5p/sirt1 axis mediating neuronal damage in Alzheimer’s disease

Period 2 protein inhibits cardiomyocyte death induced by β₁-adrenoceptor autoantibodies

Expression of circRNA-IARS in pancreatic carcinoma and its clinical significance

Expression and clinical significance of 3 kinds of circular RNA in systemic lupus erythematosus

Related Author

LU Yi

ZHOU Huadong

FU Xiaoyan

ZHOU Rui

LIU Yating

LU Jing

FENG Xiangqian

WANG Donglin

Related Institution

Department of Neurology， the First Affiliated Hospital of Bengbu Medical University

Department of Neurology， Daping Hospital， Army Medical University

Department of Neurology， Army Medical Center of PLA/Daping Hospital of Third Military Medical University

Basic Medical Research Center, School of Basic Medicine, Shanxi Medical University

Laboratory of Morphology, School of Basic Medicine, Shanxi Medical University

⁰