Ablation of the androgen receptor gene modulates atrial electrophysiology and arrhythmogenesis with calcium protein dysregulation

Wen Chin Tsai, Liang Yo Yang, Yao Chang Chen, Yu Hsun Kao, Yung Kuo Lin, Shih Ann Chen, Ching Feng Cheng, Yi Jen Chen

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

Androgen deficiency is important in the pathophysiology of atrial fibrillation. Androgen regulates cardiac electrophysiology and calcium (Ca 2+) homeostasis. The purpose of this study is to evaluate whether androgen receptor knockout (ARKO) can modulate atrial electrophysiology and arrhythmogenesiswithmodulationofCa2 +homeostasisproteins.Weusedconventional microelectrodes to study the action potential (AP) in left atrium (LA) tissues prepared from wild-type (WT)andARKOmice (aged 6-10 months) before and after the administration of isoproterenol, hypocalcemic/hypercalcemic solutions, and ouabain. Echocardiography and Western blots were used to evaluate the cardiac function and expression levels of ionic channel proteins inWTandARKOLAs.ARKOLAs had larger LA diameter with decreased LA fractional shortening than did WT LAs. In the current study, we found that ARKO LAs had a lower negative resting membrane potential and a greater 90% AP duration (APD) than did WT LAs. Isoproterenol increased the incidence and amplitude of delayed afterdepolarizations (DADs) in ARKO LAs but not in WT LAs. Hypocalcemic solutions prolonged APD in WT and ARKO LAs but increased DAD amplitude only in ARKO LAs. Hypercalcemic solutions shortened APD in ARKO LAs but not inWTLAs. Ouabain increasedDADamplitude inARKOLAs but not inWTLAs.ARKOLAs expressed higher amounts of Ca2+/calmodulin-dependent protein kinase II, Na+/Ca 2+ exchanger, and phosphorylatedphospholamban( Ser-16/Thr-17 site)andless Cav1.2, Kir2.1, Kir3.1,andKv7.1 thanWTLAs. These observationsindicatethatARKOalters atrialelectrophysiologywithincreasedatrialarrhythmogenesis.
原文英語
頁(從 - 到)2833-2842
頁數10
期刊Endocrinology
154
發行號8
DOIs
出版狀態已發佈 - 八月 1 2013

ASJC Scopus subject areas

  • Endocrinology

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