Koutsouki Evgenia, Lam Rebecca S, Seebohm Guiscard, Ureche Oana N, Ureche Liviu, Baltaev Ravshan, Lang Florian
Department of Physiology, University of Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
Biochem Biophys Res Commun. 2007 Nov 9;363(1):18-23. doi: 10.1016/j.bbrc.2007.07.181. Epub 2007 Aug 27.
Kv1.5 is expressed in multiple tissues including heart, brain, macrophages, as well as vascular, airway, and intestinal smooth muscle cells. Kv1.5 currents contribute to cardiac repolarization. In cardiac myocytes Kv1.5 colocalizes with N-cadherin. As Kv1.5 expression increases following establishment of cell-cell contacts and N-cadherin influences the activity of other ion channels, we explored whether N-cadherin participates in the regulation of Kv1.5 activity. To this end, we expressed Kv1.5 in Xenopus oocytes with or without additional expression of N-cadherin. Coexpression of N-cadherin was followed by a approximately 2- to 3-fold increase of Kv1.5 induced current. The effect of N-cadherin was not paralleled by significant alterations of Kv1.5 channel abundance within the oocyte cell membrane but resulted primarily from accelerated recovery from inactivation. In conclusion, N-cadherin modifies Kv1.5 channel activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone.
Kv1.5在多种组织中表达，包括心脏、大脑、巨噬细胞以及血管、气道和肠道平滑肌细胞。Kv1.5电流有助于心脏复极化。在心肌细胞中，Kv1.5与N-钙黏蛋白共定位。由于细胞间接触建立后Kv1.5表达增加，且N-钙黏蛋白影响其他离子通道的活性，我们探讨了N-钙黏蛋白是否参与Kv1.5活性的调节。为此，我们在非洲爪蟾卵母细胞中表达Kv1.5，同时或不额外表达N-钙黏蛋白。N-钙黏蛋白共表达后，Kv1.5诱导电流增加约2至3倍。N-钙黏蛋白的作用并非伴随着卵母细胞膜内Kv1.5通道丰度的显著改变，而是主要源于失活后恢复加速。总之，N-钙黏蛋白修饰Kv1.5通道活性，因此是参与调节包括心脏动作电位和血管张力在内的多种功能的新型候选信号分子。
