Browsing by Author "Kao, Yu-Hsun"

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Ablation of androgen receptor gene triggers right ventricular outflow tract ventricular tachycardia
(2015-06-15)
Tsai, Wen-Chin
;
Lu, Yen-Yu
;
Chen, Yao-Chang
;
Chang, Chien-Jung
;
Kao, Yu-Hsun
Background: Sex hormones and calcium (Ca2+) regulation play roles in the pathophysiology of ventricular tachycardia from right ventricular outflow tract (RVOT). The purpose of this study was to evaluate whether androgen receptor knockout (ARKO) can increase RVOT arrhythmogenesis through modulating RVOT electrophysiology and Ca2+ homeostasis. Methods: Conventional microelectrodes were used to study the action potential (AP) in RVOT tissues prepared from wild type (WT) and ARKO mice (aged 6-10 months) before and after caffeine (1 mM), isoproterenol (1 mu M), adenosine (10 mu M) and flecainide (5 mu M) administration. The Fluo-3 fluorescence Ca2+ imaging with confocal microscopy and western blots were used to investigate intracellular Ca2+ (Ca-i(2+)) transients, Ca2+ sparks, and the expressions of ionic channel proteins in ARKO and WT RVOT myocytes. Results: We found that ARKO RVOTs (n = 13) had longer AP duration, faster burst firing (5.4 +/- 0.7 vs. 3.4 +/- 0.7 Hz, P < 0.05), and higher incidence of early afterdepolarizations (82% vs. 8%, P < 0.001) than WT RVOTs (n = 11). Adenosine and flecainide can suppress caffeine-or isoproterenol-induced spontaneous rates and burst firing in WT RVOTs, but not in ARKO RVOTs. ARKO RVOT myocytes had a higher frequency (7.7 +/- 2.8 vs. 1.3 +/- 0.4 spark/mm/s, P < 0.05) and incidence (89% vs. 47%, P < 0.05) of Ca2+ sparks, and greater expressions of Cav1.2, NCX, phosphorylated RyR (s2814), phosphorylated phospholamban (Thr17), CAMKII and GRK2 than WT RVOT myocytes. However, ARKO andWT RVOT myocytes exhibit similar Ca-i(2+) transients and SR Ca2+ content, and less expression of calsequestrin. Conclusions: ARKO changes RVOT electrophysiology and Ca2+ homeostasis with increased ventricular arrhythmogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Sitagliptin Modulates the Electrical and Mechanical Characteristics of Pulmonary Vein and Atrium
(2014-01-01)
Chang, Chien-Jung
;
Yang, Ten-Fang
;
Lee, Tin-I
;
Chen, Yao-Chang
;
Kao, Yu-Hsun
Background:The pulmonary veins (PVs) and atria are important foci during that period when atrial fibrillation (AF) is generated and maintained. It is well understood that hypertension and diabetes mellitus (DM) are important risk factors for AF. Dipeptidyl peptidase-IV (DPP-4) inhibitors are new agents in the fight against type 2 DM, though they have been found to have several cardiovascular effects. However, it is not clear whether DPP-4 may modulate the electrical and mechanical characteristics in hypertensive atrium or PVs. Methods: Conventional microelectrodes were used to record the action potentials (APs) in isolated PVs, right atrium (RA), and left atrium (LA) in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) with or without sitagliptin (10 mg/kg) for 4 weeks. Results: WKY (n = 5), SHR (n =7), sitagliptin-treated WKY (n = 5) and sitagliptin-treated SHR (n = 7) had similar PV or sinoatrial spontaneous beating rates. However, the sitagliptin-treated WKY had fewer sinoatrial-PV beating rate differences than WKY, SHR or sitagliptin-treated SHR. WKY and SHR had shorter 90% (APD90) of RA AP duration than sitagliptin-treated WKY or sitagliptin-treated SHR. In contrast, WKY had longer LA APD90 than sitagliptintreated WKY, but SHR and sitagliptin-treated SHR had similar LA APD90. Sitagliptin-treated WKY or sitagliptintreated SHR had larger (RA-LA) APD90 differences than WKY or SHR, respectively. Moreover, as compared to WKY the post-rest potentiation of contraction was decreased in SHR, sitagliptin-treated WKY, and sitagliptin-treated SHR. Conclusions: Sitagliptin significantly affects the electromechanical characteristics of PVs and atria, which can be modulated by hypertension.