Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks).
Expression of multiple KCNE genes in human heart may enable variable modulation of I(Ks).
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DOI：
10.1016/j.yjmcc.2004.11.012
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发表时间：
2005-02-01
影响因子：
5
通讯作者：
George, Alfred L Jr
中科院分区：
文献类型：
--
作者：
Lundquist, Andrew L;Manderfield, Lauren J;George, Alfred L Jr
电压门控钾（K（V））通道由至少三种不同类型的蛋白质调节，包括单跨膜辅助亚基的KCNE家族。在人类基因组中，KCNE蛋白由五个基因编码，命名为KCNE 1至KCNE 5。KCNE 1在体外与KCNQ 1结合产生钾电流，与缓慢激活的延迟整流器（I（Ks））非常相似。其他KCNE蛋白也影响异源表达的KCNQ 1的活性。为了研究该基因家族在人类心脏中的潜在生理相关性，我们通过实时定量RT-PCR检测了来自代表人类心脏主要区域的正常组织的样本中KCNQ 1和所有五个KCNE基因的相对表达。KCNE基因在人心脏中表达，相对丰度排序为KCNE 1> KCNE 4> KCNE 5，大约KCNE 3>> KCNE 2。原位杂交显示KCNE 1和KCNE 3 -5在人心房肌细胞中有显著表达。在心肌病心脏中，KCNE 1、KCNE 3、KCNE 4和KCNQ 1的表达显著增加，而KCNE 2和KCNE 5的表达减少。在稳定表达KCNQ 1和KCNE 1的细胞系中，KCNE 3、KCNE 4或KCNE 5的瞬时表达显著改变了I（Ks）电流谱。即使存在额外的KCNE 1，KCNE 4和KCNE 5发挥主导作用的I（Ks）。虽然KCNE 1是在人类心脏中表达的主要KCNE家族成员，但其他KCNE转录物包括潜在的KCNQ 1抑制因子（KCNE 4和KCNE 5）的丰度及其在疾病中的表达模式改变使我们推测KCNE辅助亚基的平衡可能对心脏K（V）通道功能很重要。
Voltage-gated potassium (K(V)) channels are modulated by at least three distinct classes of proteins including the KCNE family of single transmembrane accessory subunits. In the human genome, KCNE proteins are encoded by five genes designated KCNE1 through KCNE5. KCNE1 associates with KCNQ1 in vitro to generate a potassium current closely resembling the slowly activating delayed rectifier (I(Ks)). Other KCNE proteins also affect the activity of heterologously expressed KCNQ1. To investigate the potential physiological relevance of this gene family in human heart, we examined the relative expression of KCNQ1 and all five KCNE genes in samples derived from normal tissues representing major regions of human heart by real-time, quantitative RT-PCR. KCNE genes are expressed in human heart with a relative abundance ranking of KCNE1 > KCNE4 > KCNE5 approximately KCNE3 >> KCNE2. In situ hybridization revealed prominent expression of KCNE1 and KCNE3-5 in human atrial myocytes. In cardiomyopathic hearts, expression of KCNE1, KCNE3, KCNE4, and KCNQ1 was significantly increased, while KCNE2 and KCNE5 exhibited reduced expression. In a cell line stably expressing KCNQ1 and KCNE1, transient expression of KCNE3, KCNE4, or KCNE5 significantly altered I(Ks) current profiles. Even in the presence of additional KCNE1, KCNE4 and KCNE5 exert dominant effects on I(Ks). Although KCNE1 is the predominant KCNE family member expressed in human heart, the abundance of other KCNE transcripts including potential KCNQ1 suppressors (KCNE4 and KCNE5) and their altered expression patterns in disease lead us to speculate that a balance of KCNE accessory subunits may be important for cardiac K(V) channel function.