Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
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DOI：
10.1085/jgp.200609498
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发表时间：
2006-07
影响因子：
3.8
通讯作者：
Terlau, Heinrich
中科院分区：
文献类型：
--
作者：
Finol-Urdaneta, Rocio K;Struver, Nina;Terlau, Heinrich
离子通道是跨膜蛋白，它允许离子以高速率渗透。细胞中存在的通道的动力学特性决定了细胞信号传导谱，从而决定了细胞在许多不同生理过程中的功能。我们发现来自小鼠心肌的Kv1.7通道有两个假定的翻译起始起始位点，产生两个具有不同功能特征的通道异构体mKv1.7L （489 aa）和更短的mKv1.7S （457 aa）。对mKv1.7L和mKv1.7S通道的电生理分析表明，两种通道亚型具有不同的失活动力学。由较长的蛋白质(L)形成的通道比较短的通道(S)失活得更快。我们的数据支持了mKv1.7L通道失活主要是由于n型相关机制导致的假设，该机制在mKv1.7S形式中受损。此外，只有较长的版本mKv1.7L受细胞氧化还原状态的调节，而较短的版本mKv1.7S则不受细胞氧化还原状态的调节。因此，从每个翻译起始位点开始的表达导致了显著的功能分化。我们的数据表明，mKv1.7L的氧化还原调节可能通过细胞质n端结构域的一个位点发生，该位点似乎包含与许多氧化还原敏感蛋白相似的金属配位基元。mRNA表达谱和mKv1.7动力学的氧化还原调节确定了这些通道是细胞氧化还原应激状态（如缺氧）中潜在重要的分子实体。
Ion channels are membrane-spanning proteins that allow ions to permeate at high rates. The kinetic characteristics of the channels present in a cell determine the cell signaling profile and therefore cell function in many different physiological processes. We found that Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and mKv1.7S channels revealed that the two channel isoforms have different inactivation kinetics. The channel resulting from the longer protein (L) inactivates faster than the shorter channels (S). Our data supports the hypothesis that mKv1.7L channels inactivate predominantly due to an N-type related mechanism, which is impaired in the mKv1.7S form. Furthermore, only the longer version mKv1.7L is regulated by the cell redox state, whereas the shorter form mKv1.7S is not. Thus, expression starting at each translation initiation site results in significant functional divergence. Our data suggest that the redox modulation of mKv1.7L may occur through a site in the cytoplasmic N-terminal domain that seems to encompass a metal coordination motif resembling those found in many redox-sensitive proteins. The mRNA expression profile and redox modulation of mKv1.7 kinetics identify these channels as molecular entities of potential importance in cellular redox-stress states such as hypoxia.