Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat
Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat
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DOI：
10.1161/circulationaha.106.613182
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发表时间：
2006-09-26
期刊：
影响因子：
37.8
通讯作者：
Boyett, Mark R.
中科院分区：
文献类型：
--
作者：
Yoo, Shin;Dobrzynski, Halina;Boyett, Mark R.
背景-房室结（AVN）的电活动在功能上是异质的，但这与不同的细胞类型和AVN的三维结构的关系尚不清楚。为了解决这个问题，我们已经研究了Na（V）1.5和其他Na+通道亚型的AVN.Methods和结果的表达-大鼠AVN被确定由Masson的三色染色与免疫标记蛋白：连接蛋白40，连接蛋白43，桥粒斑蛋白，心房利钠肽，超极化激活和环核苷酸门控通道4。Na+通道的表达进行了研究与亚型特异性Na+通道抗体的免疫组化。Na（v）1.1的分布方式与Na（v）1.5相似。Na（v）1.2未检出。Na（v）1.3标记存在于神经纤维和细胞体（但不是肌细胞），并在穿透房室（AV）束和共同束丰富，但在其他地区少得多。Na（v）1.5在心房肌、心室肌和左束支分支中大量表达。Na（v）1.5标记在开放结、穿透房室束、房室环束和共同束中不存在，但在下结延伸和移行区中存在降低的水平。Na（v）1.6是没有detected.Conclusions -我们的研究结果提供了多种电生理细胞类型的AV交界处的分子证据。由于Na（v）1.5突变或缺失而导致的AV传导受损一定是AVN输入（下结延伸和移行区）或输出（束支）传导受损的结果，而不是AVN本身（开放结和穿透AV）的结果束）。
Background - The electrical activity of the atrioventricular node (AVN) is functionally heterogeneous, but how this relates to distinct cell types and the 3-dimensional structure of the AVN is unknown. To address this, we have studied the expression of Na(v)1.5 and other Na+ channel isoforms in the AVN.Methods and Results - The rat AVN was identified by Masson's trichrome staining together with immunolabeling of marker proteins: connexin40, connexin43, desmoplakin, atrial natriuretic peptide, and hyperpolarization-activated and cyclic nucleotide-gated channel 4. Na+ channel expression was investigated with immunohistochemistry with isoform-specific Na+ channel antibodies. Na(v)1.1 was distributed in a similar manner to Na(v)1.5. Na(v)1.2 was not detected. Na(v)1.3 labeling was present in nerve fibers and cell bodies (but not myocytes) and was abundant in the penetrating atrioventricular (AV) bundle and the common bundle but was much less abundant in other regions. Na(v)1.5 labeling was abundant in the atrial and ventricular myocardium and the left bundle branch. Na(v)1.5 labeling was absent in the open node, penetrating AV bundle, AV ring bundle, and common bundle but present at a reduced level in the inferior nodal extension and transitional zone. Na(v)1.6 was not detected.Conclusions - Our findings provide molecular evidence of multiple electrophysiological cell types at the AV junction. Impaired AV conduction as a result of mutations in or loss of Na(v)1.5 must be the result of impaired conduction in the AVN inputs (inferior nodal extension and transitional zone) or output (bundle branches) rather than the AVN itself (open node and penetrating AV bundle).