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首页> 外文期刊>American Journal of Physiology >Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits.
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Consequences of cardiac myocyte-specific ablation of KATP channels in transgenic mice expressing dominant negative Kir6 subunits.

机译：表达显性负性Kir6亚基的转基因小鼠中心肌细胞KATP通道特异性消融的后果。

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摘要

Cardiac ATP-sensitive K+ (K(ATP)) channels are formed by Kir6.2 and SUR2A subunits. We produced transgenic mice that express dominant negative Kir6.x pore-forming subunits (Kir6.1-AAA or Kir6.2-AAA) in cardiac myocytes by driving their expression with the alpha-myosin heavy chain promoter. Weight gain and development after birth of these mice were similar to nontransgenic mice, but an increased mortality was noted after the age of 4-5 mo. Transgenic mice lacked cardiac K(ATP) channel activity as assessed with patch clamp techniques. Consistent with a decreased current density observed at positive voltages, the action potential duration was increased in these mice. Some myocytes developed EADs after isoproterenol treatment. Hemodynamic measurements revealed no significant effects on ventricular function (apart from a slightly elevated heart rate), whereas in vivo electrophysiological recordings revealed a prolonged ventricular effective refractory period in transgenic mice. The transgenic mice toleratedstress less well as evident from treadmill stress tests. The proarrhythmogenic features and lack of adaptation to a stress response in transgenic mice suggest that these features are intrinsic to the myocardium and that K(ATP) channels in the myocardium have an important role in protecting the heart from lethal arrhythmias and adaptation to stress situations.
机译：心脏ATP敏感的K +（K（ATP））通道是由Kir6.2和SUR2A亚基形成的。我们生产的转基因小鼠通过用α-肌球蛋白重链启动子驱动表达，在心肌细胞中表达显性阴性Kir6.x孔形成亚基（Kir6.1-AAA或Kir6.2-AAA）。这些小鼠出生后的体重增加和发育与非转基因小鼠相似，但在4-5 mo的年龄后发现死亡率增加。转基因小鼠缺乏膜片钳技术评估的心脏K（ATP）通道活性。与在正电压下观察到的电流密度降低一致，这些小鼠的动作电位持续时间增加了。异丙肾上腺素治疗后，一些心肌细胞会产生EAD。血液动力学测量显示对心室功能无明显影响（除心率略有升高外），而体内电生理学记录显示转基因小鼠的心室有效不应期延长。从跑步机压力测试中可以明显看出，转基因小鼠对压力的耐受性较差。转基因小鼠的促心律失常特征和对压力反应的适应性不足表明这些特征是心肌固有的，并且心肌中的K（ATP）通道在保护心脏免受致命性心律失常和适应压力情况方面具有重要作用。

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