Expression and alteration of BKCa channels in the sphincter of Oddi's from rabbits with hypercholesterolemia

IF 3.3 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Channels Pub Date : 2017-01-19 DOI:10.1080/19336950.2017.1279369

Dan Feng, Haiyan Nan, Wen Wang, Linfeng Yan, Pang Du, Lin Zuo, Kun Zhang, Minggao Zhao, G. Cui

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引用次数: 1

Abstract

ABSTRACT This study aimed to investigate the expression and function of BKCa channels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into 2 groups: the control group was fed standard chow (n = 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n = 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups. Although the total protein expression of BKCa α- and β1-subunit was not significantly different between the control and HC groups, the Tyr-phosphorylation of BKCa α-subunit was significantly decreased in the HC group than in the control group. In addition, hypercholesterolemia significantly increased Acetylcholine (ACh)-induced contraction of the SO rings. Pretreatment with 30 μM NS1619, a BKCa channel agonist, significantly reduced ACh-induced contraction of the SO rings in HC rabbits. Moreover, pretreatment with 100 μM Na3OV4, a protein tyrosine phosphatase inhibitor, significantly reduced ACh-induced contraction of the SO rings in HC rabbits, whereas it significantly increased upon pretreating with 10 μM Genistein, a tyrosine kinase inhibitor. Whole-cell patch clamp recordings showed that BKCa current density was significantly lower in SOSMCs from HC group than that from control group. Our findings suggest that hypercholesterolemia-induced downregulation of BKCa channel, and Tyr-phosphorylation of BKCa α-subunit may contribute to the hyperresponsiveness of the SO ring in HC rabbits.

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高胆固醇血症家兔Oddi氏括约肌BKCa通道的表达和改变

本研究旨在探讨高胆固醇血症(HC)兔Oddi括约肌(SO)中BKCa通道的表达和功能。将新西兰大白兔随机分为2组，对照组饲喂标准饲料(n = 18)，高胆固醇组饲喂含1.5%胆固醇的高胆固醇饲料(n = 18)。HC组的血清胆固醇水平显著高于对照组，但体重在对照组和HC组之间无显著差异。虽然BKCa α-和β1亚基的总蛋白表达量在对照组和HC组之间无显著差异，但BKCa α-亚基的tyr1磷酸化水平在HC组明显低于对照组。此外，高胆固醇血症显著增加乙酰胆碱(ACh)诱导的SO环收缩。预处理30 μM NS1619 (BKCa通道激动剂)可显著降低HC兔ach诱导的SO环收缩。此外，100 μM Na3OV4(蛋白酪氨酸磷酸酶抑制剂)预处理可显著降低HC兔ach诱导的SO环收缩，而10 μM Genistein(酪氨酸激酶抑制剂)预处理可显著增加HC兔ach诱导的SO环收缩。全细胞膜片钳记录显示，HC组SOSMCs的BKCa电流密度明显低于对照组。我们的研究结果表明，高胆固醇血症诱导的BKCa通道下调和BKCa α-亚基的tyr1磷酸化可能是HC兔SO环高反应性的原因之一。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Channels 生物-生化与分子生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Channels is an open access journal for all aspects of ion channel research. The journal publishes high quality papers that shed new light on ion channel and ion transporter/exchanger function, structure, biophysics, pharmacology, and regulation in health and disease. Channels welcomes interdisciplinary approaches that address ion channel physiology in areas such as neuroscience, cardiovascular sciences, cancer research, endocrinology, and gastroenterology. Our aim is to foster communication among the ion channel and transporter communities and facilitate the advancement of the field.