Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals.
Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals.
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DOI：
10.1016/j.yjmcc.2007.07.062
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发表时间：
2007-11-01
影响因子：
5
通讯作者：
Isom, Lori L
中科院分区：
文献类型：
--
作者：
Lopez-Santiago, Luis F;Meadows, Laurence S;Isom, Lori L
在神经元中，电压门控钠通道β亚单位调节钠通道α亚单位的表达水平、亚细胞定位和电生理特性。然而，β亚基对心脏钠通道功能的贡献尚不清楚。我们用Scn1b缺失小鼠检测了β 1在心脏兴奋性中的作用。与野生型小鼠相比，在自主神经阻滞前后，Scn1b缺失小鼠的心电图显示更长的RR间期和更长的QT(c)间期。在急性分离的心室肌细胞中，β 1表达的缺失导致峰值和持续钠电流增加约1.6倍，而通道门控和动力学不受影响。Na(v)1.5在空白肌细胞中的表达增加约1.3倍。急性分离心室肌细胞的动作电位记录显示复极减慢，支持QT(c)间期延长。单个肌细胞或心室切片的免疫染色显示，钠通道α或β亚基、锚蛋白(B)、锚蛋白(G)、n-钙粘蛋白或连接蛋白43的定位没有明显的改变。综上所述，这些结果表明beta1对正常心脏兴奋性至关重要，而beta1的缺失可能与长QT表型相关。
In neurons, voltage-gated sodium channel beta subunits regulate the expression levels, subcellular localization, and electrophysiological properties of sodium channel alpha subunits. However, the contribution of beta subunits to sodium channel function in heart is poorly understood. We examined the role of beta1 in cardiac excitability using Scn1b null mice. Compared to wildtype mice, electrocardiograms recorded from Scn1b null mice displayed longer RR intervals and extended QT(c) intervals, both before and after autonomic block. In acutely dissociated ventricular myocytes, loss of beta1 expression resulted in a approximately 1.6-fold increase in both peak and persistent sodium current while channel gating and kinetics were unaffected. Na(v)1.5 expression increased in null myocytes approximately 1.3-fold. Action potential recordings in acutely dissociated ventricular myocytes showed slowed repolarization, supporting the extended QT(c) interval. Immunostaining of individual myocytes or ventricular sections revealed no discernable alterations in the localization of sodium channel alpha or beta subunits, ankyrin(B), ankyrin(G), N-cadherin, or connexin-43. Together, these results suggest that beta1 is critical for normal cardiac excitability and loss of beta1 may be associated with a long QT phenotype.