Enhancement of sodium current contributes to the maintenance of conduction velocity in the aging myocardium

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of molecular and cellular cardiology Pub Date : 2025-07-17 DOI:10.1016/j.yjmcc.2025.07.013

E.V. Minnebaeva , M.A. Gonotkov , A.V. Durkina , E.A. Lebedeva , A.V. Fedorov , M.A. Chelombitko , O.B. Pustovit , T.S. Filatova , J.E. Azarov , O.G. Bernikova

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引用次数: 0

Abstract

Introduction

The aging myocardium undergoes significant electrophysiological and structural remodeling. These complex alterations may affect conduction velocity (CV), whose age-related changes remain unclear. This study aims at evaluation of the CV changes in the rats of different ages and assessment of the contribution of cellular and tissue factors into CV.

Methods

The CV was determined in 3-, 12- and 24-month-old anesthetized rats using epicardial mapping under ventricular stimulation. The contribution of gap junction functionality to CV was assessed using carbenoxolone, an uncoupling agent for Cx43. The measurement of sodium ion current (I_Na) was performed in isolated ventricular cardiomyocytes using the patch-clamp technique. Expression of gene transcripts encoding Cx43 (GJA1a) and sodium currents (SCN5a) were assessed using RT-PCR analysis.

Results

The baseline longitudinal conduction velocity (CV_L) did not differ between 3-, 12- and 24-month-old groups. Intravenous administration of carbenoxolone decreased the CV_L only in the 3-month-old animals. The density of sodium current (I_Na) of 24-month-old rats was greater as compared to 3-month-old rats. The extent of fibrosis was less prominent in 3-month-old rats than in the older animals. The expression of SCN5a gene transcripts was increased and expression of GJA1a was decreased in the 24-month-old rats.

Conclusions

The enhancement of sodium current preserves conduction velocity despite impaired connexin function and increased fibrosis in the aging myocardium.

Abstract Image

查看原文本刊更多论文

钠电流的增强有助于维持老化心肌的传导速度。

导读：衰老心肌发生显著的电生理和结构重构。这些复杂的改变可能影响传导速度（CV），其与年龄相关的变化尚不清楚。本研究旨在评估不同年龄大鼠的CV变化，并评估细胞和组织因素对CV的贡献。方法：采用心外膜标测法测定3、12、24月龄麻醉大鼠心室刺激下的心外膜CV。使用卡贝诺洛酮（Cx43的解偶联剂）评估间隙连接功能对CV的贡献。采用膜片钳技术在离体心室心肌细胞中测量钠离子电流（INa）。采用RT-PCR分析Cx43 （GJA1a）和钠电流（SCN5a）基因转录本的表达情况。结果：基线纵向传导速度（CVL）在3、12、24月龄组间无差异。静脉注射卡贝诺洛酮仅在3个月大的动物中降低CVL。24月龄大鼠钠电流密度（INa）高于3月龄大鼠。3个月大的大鼠的纤维化程度不如老年大鼠明显。24月龄大鼠SCN5a基因转录本表达增加，GJA1a表达降低。结论：尽管连接蛋白功能受损，纤维化增加，但钠电流的增强可保持心肌的传导速度。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of molecular and cellular cardiology 医学-细胞生物学

CiteScore

10.70

自引率

0.00%

发文量

171

审稿时长

42 days

期刊介绍： The Journal of Molecular and Cellular Cardiology publishes work advancing knowledge of the mechanisms responsible for both normal and diseased cardiovascular function. To this end papers are published in all relevant areas. These include (but are not limited to): structural biology; genetics; proteomics; morphology; stem cells; molecular biology; metabolism; biophysics; bioengineering; computational modeling and systems analysis; electrophysiology; pharmacology and physiology. Papers are encouraged with both basic and translational approaches. The journal is directed not only to basic scientists but also to clinical cardiologists who wish to follow the rapidly advancing frontiers of basic knowledge of the heart and circulation.