Connexin40 and connexin43 determine gating properties of atrial gap junction channels.
Connexin40 and connexin43 determine gating properties of atrial gap junction channels.
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DOI：
10.1016/j.yjmcc.2009.05.014
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发表时间：
2010-01
影响因子：
5
通讯作者：
Veenstra, Richard D.
中科院分区：
文献类型：
--
作者：
Lin, Xianming;Gemel, Joanna;Glass, Aaron;Zemlin, Christian W.;Beyer, Eric C.;Veenstra, Richard D.
虽然心室缝隙连接只包含Cx43，心房缝隙连接包含Cx40和Cx43，但这种共表达的功能后果仍然知之甚少。我们定量了Cx40和Cx43的表达及其对心房缝隙连接传导（gj）的贡献。新生鼠心房肌细胞显示出相似的Cx40和Cx43蛋白丰度，而心室肌细胞含有的Cx43至少是Cx40的20倍。由于Cx40间隙连接通道被2 mM精胺阻断，而Cx43通道不受影响，因此我们使用精胺阻断作为功能性双全细胞膜片钳测定来确定Cx40对心脏gj的贡献。略多于一半的心房gj和≤20%的心室gj被抑制。在Cx40基因敲除小鼠的心肌细胞中，心室gj的抑制被完全消除，心房gj的阻滞减少至<20%。与心室间隙连接相比，心房gj的跨接电压（Vj）依赖性失活减少，动力学减慢，而快速和缓慢失活的Vj依赖性不变。结论：Cx40和Cx43在心房中同样丰富，对心房gj的贡献相似。Cx40的共表达解释了心房和心室之间Vj依赖性门控特性的大部分（但不是全部）差异，这些差异可能在缓慢心肌传导和心律失常的发生中发挥作用。
While ventricular gap junctions contain only Cx43, atrial gap junctions contain both Cx40 and Cx43; yet the functional consequences of this co-expression remain poorly understood. We quantitated the expression of Cx40 and Cx43 and their contributions to atrial gap junctional conductance (gj). Neonatal murine atrial myocytes showed similar abundances of Cx40 and Cx43 proteins, while ventricular myocytes contained at least 20 times more Cx43 than Cx40. Since Cx40 gap junction channels are blocked by 2 mM spermine while Cx43 channels are unaffected, we used spermine block as a functional dual whole cell patch clamp assay to determine Cx40 contributions to cardiac gj. Slightly more than half of atrial gj and ≤20% of ventricular gj were inhibited. In myocytes from Cx40 null mice, the inhibition of ventricular gj was completely abolished, and the block of atrial gj was reduced to < 20%. Compared to ventricular gap junctions, the transjunctional voltage (Vj)-dependent inactivation of atrial gj was reduced and kinetically slowed, while the Vj-dependence of fast and slow inactivation was unchanged. We conclude that Cx40 and Cx43 are equally abundant in atrium and make similar contributions to atrial gj. Co-expression of Cx40 accounts for most, but not all, of the differences in the Vj-dependent gating properties between atrium and ventricle that may play a role in the genesis of slow myocardial conduction and arrhythmias.
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影响因子：
10.8
作者：
Lin, Xianming;Zemlin, Christian;Veenstra, Richard D.
通讯作者：
Veenstra, Richard D.
影响因子：
20.1
作者：
Lin, XM;Crye, M;Veenstra, RD
通讯作者：
Veenstra, RD
影响因子：
4.8
作者：
Gong, Xiang-Qun;Shao, Qing;Laird, Dale W.
通讯作者：
Laird, Dale W.
DOI：
10.1152/ajpheart.00943.2003
发表时间：
2004-05-01
影响因子：
4.8
作者：
Lin, XM;Veenstra, RD
通讯作者：
Veenstra, RD
影响因子：
20.1
作者：
BEBLO, DA;WANG, HZ;VEENSTRA, RD
通讯作者：
VEENSTRA, RD