Heterogeneous functional expression of the sustained inward Na+ current in guinea pig sinoatrial node cells
Heterogeneous functional expression of the sustained inward Na+ current in guinea pig sinoatrial node cells
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DOI：
10.1007/s00424-017-2091-y
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发表时间：
2018-03-01
影响因子：
4.5
通讯作者：
Matsuura, Hiroshi
中科院分区：
文献类型：
--
作者：
Toyoda, Futoshi;Ding Wei-Guang;Matsuura, Hiroshi
窦房结 (SAN) 细胞中持续的内向 Na+ 电流 (I (st)) 被认为在心脏起搏中发挥着关键作用。然而，SAN 中的细胞组成是异质的，并且 I (st) 大小的细胞间变异性仍有待充分表征。本研究调查了从豚鼠 SAN 分离的形态不同类型的起搏细胞中 I (st) 的电流密度。 I (st)优先在自发活动的纺锤体或蜘蛛状细胞中检测到，但在较大尺寸的细长纺锤型细胞中表达较差，并且在明显横纹的心房样细胞中几乎不存在，尽管有趣电流（I (f)）有清晰的表达。纺锤体细胞和蜘蛛细胞中的I(st)电流密度在0.7至1.6 pA pF(-1)之间变化，并且在具有相似形态的非搏动细胞中显着降低。通过线性回归分析，我们发现 I (st) 电流密度与 L 型 Ca2+ 电流 (I (Ca,L)) 之间存在正相关关系，这一点在纺锤体细胞和蜘蛛细胞中特别观察到。这些细胞在半最大 I (Ca,L) 激活方面表现出比心房样细胞更大的负电压，表明 SAN 细胞中 Ca(V)1.2 和 Ca(V)1.3 介导的 I (Ca,L) 之间存在可变比率。一致的单细胞转录测量结果证实，梭形细胞中的 Ca(V)1.3 的相对表达量高于心房样细胞，该细胞在更多的负电位下激活。综上所述，这些结果可以解释为表明 I (st) 在原代起搏细胞中发挥特定作用，并且它的存在与 Ca(V)1.3 介导的 I (Ca,L) 的功能水平密切相关。
The sustained inward Na+ current (I (st)) identified in the sinoatrial node (SAN) cell has been suggested to play a pivotal role in cardiac pacemaking. However, the composition of cells in the SAN is heterogeneous and cell-to-cell variability in the magnitude of I (st) remains to be fully characterized. The present study investigated the current density of I (st) in morphologically different types of pacemaker cells dissociated from guinea pig SAN. I (st) was preferentially detected in spontaneously active spindle or spider-shaped cells, but was less well expressed in larger-sized elongated spindle-type cells and practically absent in clearly striated atrial-like cells, despite clear expression of the funny current (I (f)). The current density of I (st) in spindle and spider cells varied from 0.7 to 1.6 pA pF(-1) and was significantly reduced in non-beating cells with similar morphologies. By linear regression analysis, we identified a positive correlation between the current densities of I (st) and the L-type Ca2+ current (I (Ca,L)), which was specifically observed in spindle and spider cells. These cells exhibited a more negative voltage for half maximal I (Ca,L) activation than atrial-like cells, suggesting a variable ratio between Ca(V)1.2- and Ca(V)1.3-mediated I (Ca,L) in SAN cells. Consistent single-cell transcript measurements confirmed a higher relative expression of Ca(V)1.3, which activates at more negative potentials, in spindle cells than in atrial-like cells. Taken together, these results can be interpreted as indicating that I (st) plays a specific role in primary pacemaker cells and that its presence is closely correlated with functional levels of Ca(V)1.3-mediated I (Ca,L).