Pérez-Verdaguer Mireia, Capera Jesusa, Serrano-Novillo Clara, Estadella Irene, Sastre Daniel, Felipe Antonio
a Molecular Physiology Laboratory, Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina (IBUB) , Universitat de Barcelona , Barcelona , Spain.
Expert Opin Ther Targets. 2016;20(5):577-91. doi: 10.1517/14728222.2016.1112792. Epub 2015 Dec 4.
The voltage-dependent potassium channel Kv1.3 is mainly present in the nervous and immune systems. In leukocytes, Kv1.3 fine-tunes the activation and proliferation of the immune response. However, Kv1.3 is also present in other tissues where its physiological role is still under investigation. Thus, Kv1.3 alterations have been related to several human diseases.
In this work, the authors highlight the role of Kv1.3 in various pathologies and the potential use of Kv1.3 blockers as safe pharmacological tools. The limited repertoire of K(+) channels in leukocytes and its expression pattern makes Kv1.3 crucial for effector memory T cell physiology and it is therefore a good pharmacological target for chronic inflammatory diseases. Moreover, Kv1.3 has been related to insulin sensitivity, cell proliferation and apoptosis. In this scenario, Kv1.3 activity is also implicated in non-insulin-dependent type II diabetes mellitus, obesity and cancer.
Fortunately, Kv1.3 is characterized by a very selective and potent pharmacology that has been demonstrated to ameliorate autoimmune and metabolic symptoms in disease-animal models without major side effects. Moreover, Kv1.3 blockers are showing positive results in preclinical trials. Considering this evidence, the implication of Kv1.3 in a wide repertoire of human pathologies indicates this channel is an important therapeutic target.
电压依赖性钾通道Kv1.3主要存在于神经和免疫系统中。在白细胞中,Kv1.3可微调免疫反应的激活和增殖。然而,Kv1.3也存在于其他组织中,其生理作用仍在研究中。因此,Kv1.3的改变与多种人类疾病有关。
在这项工作中,作者强调了Kv1.3在各种病理中的作用以及Kv1.3阻滞剂作为安全药理学工具的潜在用途。白细胞中钾通道种类有限及其表达模式使Kv1.3对效应记忆T细胞生理功能至关重要,因此它是慢性炎症性疾病的良好药理学靶点。此外,Kv1.3与胰岛素敏感性、细胞增殖和凋亡有关。在这种情况下,Kv1.3的活性也与非胰岛素依赖型II型糖尿病、肥胖症和癌症有关。
幸运的是,Kv1.3具有非常选择性和强效的药理学特性,已证明在疾病动物模型中可改善自身免疫和代谢症状,且无重大副作用。此外,Kv1.3阻滞剂在临床前试验中显示出积极结果。考虑到这些证据,Kv1.3在多种人类疾病中的作用表明该通道是一个重要的治疗靶点。