小电导钙激活钾通道是压力诱导内皮功能障碍的原因之一。

IF 2.9 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Microvascular research Pub Date : 2024-06-18 DOI:10.1016/j.mvr.2024.104699

Zhen Yang , Yingrui Li , Mengying Huang , Xin Li , Xuehui Fan , Chen Yan , Zenghui Meng , Bin Liao , Nazha Hamdani , Ibrahim El-Battrawy , Xiaoli Yang , Xiaobo Zhou , Ibrahim Akin

{"title":"小电导钙激活钾通道是压力诱导内皮功能障碍的原因之一。","authors":"Zhen Yang , Yingrui Li , Mengying Huang , Xin Li , Xuehui Fan , Chen Yan , Zenghui Meng , Bin Liao , Nazha Hamdani , Ibrahim El-Battrawy , Xiaoli Yang , Xiaobo Zhou , Ibrahim Akin","doi":"10.1016/j.mvr.2024.104699","DOIUrl":null,"url":null,"abstract":"<div>Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (ISK1–3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of ISK1–3. H2O2 enhanced ISK1–3 and ET-1 production. Enhancing ISK1–3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.</div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"155 ","pages":"Article 104699"},"PeriodicalIF":2.9000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000487/pdfft?md5=5a77f3e9f848d1582231b15caec297a0&pid=1-s2.0-S0026286224000487-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Small conductance calcium-activated potassium channel contributes to stress induced endothelial dysfunctions\",\"authors\":\"Zhen Yang , Yingrui Li , Mengying Huang , Xin Li , Xuehui Fan , Chen Yan , Zenghui Meng , Bin Liao , Nazha Hamdani , Ibrahim El-Battrawy , Xiaoli Yang , Xiaobo Zhou , Ibrahim Akin\",\"doi\":\"10.1016/j.mvr.2024.104699\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (ISK1–3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of ISK1–3. H2O2 enhanced ISK1–3 and ET-1 production. Enhancing ISK1–3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.</div>\",\"PeriodicalId\":18534,\"journal\":{\"name\":\"Microvascular research\",\"volume\":\"155 \",\"pages\":\"Article 104699\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-06-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0026286224000487/pdfft?md5=5a77f3e9f848d1582231b15caec297a0&pid=1-s2.0-S0026286224000487-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Microvascular research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0026286224000487\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Microvascular research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0026286224000487","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}

引用次数: 0

摘要

塔克次氏综合征患者表现出内皮功能障碍，但其潜在机制尚未完全阐明。本研究旨在探索儿茶酚胺过量诱导内皮功能障碍的分子信号。用肾上腺素挑战人心脏微血管内皮细胞，模拟儿茶酚胺过量。研究采用了膜片钳、FACS、ELISA、PCR 和免疫染色法。肾上腺素（Epi）通过激活α1肾上腺素受体增强了小电导钙激活钾通道电流（ISK1-3）。苯肾上腺素增强了去甲斑鸠素-1（ET-1）和活性氧（ROS）的产生，其效应涉及 ISK1-3 的贡献。H2O2 增强了 ISK1-3 和 ET-1 的产生。增强 ISK1-3 会导致超极化，从而增加 ROS 和 ET-1 的产生。BAPTA 部分降低了苯肾上腺素诱导的 ET-1 和 ROS 的增强，表明α1 受体激活可通过钙依赖和钙不依赖两种方式增强 ROS/ET-1 的生成。该研究表明，高浓度儿茶酚胺可通过α1受体-ROS信号激活SK1-3通道，增加ET-1的产生，从而促进血管收缩。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Small conductance calcium-activated potassium channel contributes to stress induced endothelial dysfunctions

查看原文本刊更多论文

Small conductance calcium-activated potassium channel contributes to stress induced endothelial dysfunctions

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction.

Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study.

Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (I_SK1_–₃) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of I_SK1_–₃. H₂O₂ enhanced I_SK1_–₃ and ET-1 production. Enhancing I_SK1_–₃ caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways.

The study demonstrates that high concentration catecholamine can activate SK1–3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Microvascular research 医学-外周血管病

CiteScore

6.00

自引率

3.20%

发文量

158

审稿时长

43 days

期刊介绍： Microvascular Research is dedicated to the dissemination of fundamental information related to the microvascular field. Full-length articles presenting the results of original research and brief communications are featured. Research Areas include: • Angiogenesis • Biochemistry • Bioengineering • Biomathematics • Biophysics • Cancer • Circulatory homeostasis • Comparative physiology • Drug delivery • Neuropharmacology • Microvascular pathology • Rheology • Tissue Engineering.