构建支架以降低血压。

Scaffolding builds to reduce blood pressure.

作者信息

Bagher Pooneh, Garland Christopher J

机构信息

Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.

Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK

出版信息

Sci Signal. 2014 Jul 8;7(333):pe16. doi: 10.1126/scisignal.2005527.

DOI:10.1126/scisignal.2005527

PMID:25005227

Abstract

Endothelial cells provide vasodilator signals to reduce blood pressure. In the small resistance arteries and arterioles, which determine the distribution and pressure of blood, the major signal is hyperpolarization reflecting the endothelial activity of calcium-activated potassium channels (KCa). In this issue of Science Signaling, Sonkusare et al. report that the scaffold protein AKAP150 is required for the kinase PKC and the calcium channel TRPV4 to enable receptor-mediated relaxation signaling. This scaffold enhances TRPV4 gating cooperativity and markedly amplifies the Ca(2+) signal, which ultimately activates (mainly) IKCa channels. Normally restricted to tiny endothelial projections, AKAP150 localization and associated signaling is disrupted in a model of hypertension, thereby diminishing hyperpolarization and vasodilation.

摘要

内皮细胞提供血管舒张信号以降低血压。在决定血液分布和压力的小阻力动脉和微动脉中，主要信号是超极化，反映了钙激活钾通道（KCa）的内皮活性。在本期《科学信号》中，索尼库雷等人报告称，支架蛋白AKAP150是激酶PKC和钙通道TRPV4实现受体介导的舒张信号所必需的。这种支架增强了TRPV4门控协同性，并显著放大了Ca(2+)信号，最终（主要）激活IKCa通道。AKAP150的定位和相关信号通常局限于微小的内皮突起，在高血压模型中会被破坏，从而减少超极化和血管舒张。