Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs
Role of ion channels in sepsis-induced atrial tachyarrhythmias in guinea pigs
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DOI：
10.1111/j.1476-5381.2011.01769.x
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发表时间：
2012-05-01
影响因子：
7.3
通讯作者：
Yamazaki, Mitsuaki
中科院分区：
文献类型：
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作者：
Aoki, Yuta;Hatakeyama, Noboru;Yamazaki, Mitsuaki
背景和目的在败血症患者中偶尔会观察到室上性快速性心律失常，包括房颤。脓毒症对心脏离子通道功能和表达的调节可能在快速性心律失常的发生中起作用。300亩g.kg（-1））。用全细胞膜片钳方法测定了LPS后10 h豚鼠心房肌细胞的膜电位和离子电流。这与L-型Ca ~（2+）电流减少和延迟整流钾电流增加有关。当L-硝基精氨酸甲酯（L-NAME）或S-乙基异硫脲与LPS同时作用时，上述电生理变化被消除。在LPS处理的动物的心房组织中，Ca 2+通道亚单位（Ca（v）1.2和Ca（v）1.3）减少，延迟整流K+通道亚单位（K（v）11.1和K（v）7.1）增加。然而，L-NAME治疗并没有实质上逆转LPS治疗动物心房表达的这种变化，除了K（v）11.1亚基恢复到对照水平。LPS注射后，诱导型NOS在心房组织上调，心房NO的生产明显increased.CONCLUSIONS和意义在心房肌细胞从豚鼠脓毒症，APD显着缩短。这可能反映了离子通道的硝化作用，这将改变通道功能，而不是心房通道表达的变化。APD缩短可能是脓毒症发生房性快速心律失常的机制之一。
BACKGROUND AND PURPOSE Supraventricular tachyarrhythmias, including atrial fibrillation, are occasionally observed in patients suffering from sepsis. Modulation of cardiac ion channel function and expression by sepsis may have a role in the genesis of tachyarrhythmias.EXPERIMENTAL APPROACH Sepsis was induced by LPS (i.p.; 300 mu g.kg(-1)) in guinea pigs. Membrane potentials and ionic currents were measured in atrial myocytes isolated from guinea pigs 10 h after LPS, using whole cell patch-clamp methods.KEY RESULTS In atrial cells from LPS-treated animals, action potential duration (APD) was significantly shortened. It was associated with a reduced L-type Ca2+ current and an increased delayed rectifier K+ current. These electrophysiological changes were eliminated when N-G-nitro-L-arginine methyl ester (L-NAME) or S-ethylisothiourea was given together with LPS. In atrial tissues from LPS-treated animals, Ca2+ channel subunits (Ca(v)1.2 and Ca(v)1.3) decreased and delayed rectifier K+ channel subunits (K(v)11.1 and K(v)7.1) increased. However, L-NAME treatment did not substantially reverse such changes in atrial expression in LPS-treated animals, with the exception that K(v)11.1 subunits returned to control levels. After LPS injection, inducible NOS in atrial tissues was up-regulated, and atrial NO production clearly increased.CONCLUSIONS AND IMPLICATIONS In atrial myocytes from guinea pigs with sepsis, APD was significantly shortened. This may reflect nitration of the ion channels which would alter channel functions, rather than changes in atrial expression of the channels. Shortening of APD could serve as one of the mechanisms underlying atrial tachyarrhythmia in sepsis.