Expression of connexin 43, ion channels and Ca2+-handling proteins in rat pulmonary vein cardiomyocytes

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF is thought to be triggered by ectopic beats, originating primarily in the myocardial sleeves surrounding the pulmonary veins (PVs). The mechanisms underlying these cardiac arrhythmias remain unclear. To investigate this, frozen sections of heart and lung tissue from adult rats without arrhythmia were obtained in different planes, stained with Masson's trichrome, and immunolabeled for connexin 43 (Cx43), caveolin-3 (Cav3), hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), Nav1.5, Kir2.1, and the calcium handling proteins sarcoplasmic/endoplasmic reticulum calcium-ATPase 2a (SERCA2a) and ryanodine receptor 2 (RyR2). Transverse sections offered the best view of the majority of the PVs in the tissue samples. Cx43 was observed to be expressed throughout the atria, excluding the sinoatrial and atrioventricular nodes, and in the myocardial sleeves of the PVs. In contrast, HCN4 was only expressed in the sinoatrial and atrioventricular nodes. The immunodensity of Cav3, Nav1.5, Kir2.1, SERCA2a and RyR2 in the PVs imaged was similar to that in atria. The results suggest that in the absence of arrhythmia, the investigated molecular properties of the ion channels of rat PV cardiomyocytes resemble those of the working myocardium. This indicates that ectopic beats originating in the myocardial sleeves of the PVs occur only under pathological conditions.

Spontaneous Ca2+ transients in rat pulmonary vein cardiomyocytes are increased in frequency and become more synchronous following electrical stimulation

“…In pulmonary vein cardiomyocytes, RyRs had a striated arrangement, which is in agreement with previous studies in the rat [33] and mouse [17]. However, this study is the first to demonstrate that RyRs also have a junctional distribution along the periphery of pulmonary vein cardiomyocytes, similar to that observed in rat atrial cardiomyocytes [34,35].…”

Connexin 43 reduces susceptibility to sympathetic atrial fibrillation

“…In the heart, connexins mediate electrical coupling among cardiac myocytes to form signal channels, allowing for the transmission of electrical waves that are responsible for synchronized contraction among tissues (6). connexin 43 (cx43), a member of the connexins family, is most abundantly expressed in the cardiac muscle (7). cx43 has been demonstrated to serve a role in a number of diseases, including oral squamous cell carcinoma, pancreatic cancer, prostate cancer, acute myeloid leukemia, myocardial edema, vascular restenosis and Parkinson's disease (8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Metoprolol protects cardiomyocytes in rabbit model of heart failure by regulating Cx43

“…ImageJ software was used to analyze the average positive expression area and integral optical density of the image. The method of the calculation of the average positive expression area: the number of Cx43 positive gap junctions of 6 visual fields was counted and the total number was calculated, finally, the positive area of 6 visual fields was measured ( 9 ).…”