Mays D J, Foose J M, Philipson L H, Tamkun M M
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Clin Invest. 1995 Jul;96(1):282-92. doi: 10.1172/JCI118032.
The cloned Kv1.5 K+ channel displays similar kinetics and pharmacology to a delayed rectifier channel found in atrial myocytes. To determine whether the Kv1.5 isoform plays a role in the cardiac action potential, it is necessary to confirm the expression of this channel in cardiac myocytes. Using antibodies directed against two distinct channel epitopes, the Kv1.5 isoform was localized in human atrium and ventricle. Kv1.5 was highly localized at intercalated disk regions as determined by colocalization with connexin and N-cadherin specific antibodies. While both antichannel antibodies localized the Kv1.5 protein in cardiac myocytes, only the NH2-terminal antibodies stained vascular smooth muscle. The selective staining of vasculature by this antiserum suggests that epitope accessibility, and perhaps channel structure, varies between cardiac and vascular myocytes. Kv1.5 expression was localized less in newborn tissue, with punctate antibody staining dispersed on the myocyte surface. This increasing organization with age was similar to that observed for connexin. Future work will address whether altered K+ channel localization is associated with cardiac disease in addition to changing with development.
克隆的Kv1.5钾离子通道表现出与心房肌细胞中发现的延迟整流通道相似的动力学和药理学特性。为了确定Kv1.5亚型是否在心脏动作电位中起作用，有必要证实该通道在心肌细胞中的表达。使用针对两个不同通道表位的抗体，Kv1.5亚型定位于人的心房和心室。通过与连接蛋白和N-钙黏着蛋白特异性抗体共定位确定，Kv1.5高度定位于闰盘区域。虽然两种抗通道抗体都将Kv1.5蛋白定位于心肌细胞中，但只有氨基末端抗体能对血管平滑肌进行染色。该抗血清对脉管系统的选择性染色表明，心脏和血管肌细胞之间表位的可及性以及可能的通道结构有所不同。Kv1.5在新生组织中的表达较少，点状抗体染色分散在心肌细胞表面。这种随年龄增长而增加的组织化与连接蛋白的情况相似。未来的工作将探讨钾离子通道定位的改变除了随发育变化外，是否还与心脏疾病有关。
