Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K+ channels
Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K+ channels
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DOI：
10.1016/s0008-6363(02)00661-2
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发表时间：
2003-02-01
影响因子：
10.8
通讯作者：
Duff, HJ
中科院分区：
文献类型：
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作者：
Dong, D;Duan, YJ;Duff, HJ
背景：钙调神经磷酸酶在转基因小鼠中的过度表达可导致心脏肥大和意外死亡。方法和结果：没有TG存活超过24周（n=38），而所有野生型（WT，n=47）存活。复极延长先于持续性多形性室性心动过速和高度房室传导阻滞的发展，这发生在自发性猝死期间。由于去极化激活的K+通道在小鼠的复极中占主导地位，我们假设TG会降低这些K+电流，并且体内给予钙调磷酸酶抑制剂环孢素A（CsA）会降低这种效应。CsA逆转心肌肥大：WT左心室肌细胞的电容测量值（127+/-7 pF; n=45）和CsA治疗的TG（129+/-14 pF; n=17）显著低于安慰剂治疗的TG（220+/-11 pF; n=41; P
Background: Overexpression of calcineurin in transgenic (TG) mice results in cardiac hypertrophy and unexpected deaths. Methods and results: None of the TG survived beyond 24 weeks (n=38) whereas all of the wildtype (WT, n=47) survived. Prolongation of repolarization preceded the development of sustained pleomorphic ventricular tachycardia and high degree atrioventricular block, which occurred during spontaneous sudden deaths. Since depolarization-activated K+ channels contribute dominantly to repolarization in mice, we hypothesized that the TG would decrease these K+ currents and that the in vivo administration of cyclosporin A (CsA), a calcineurin inhibitor, would reduce this effect. CsA reversed cardiac hypertrophy: capacitance measurements of WT left ventricular myocytes (127+/-7 pF; n=45) and CsA-treated TG (129+/-14 pF; n=17) were significantly lower than in placebo-treated TG (220+/-11 pF; n=41; P