Beta-adrenergic stimulation reverses the I Kr-I Ks dominant pattern during cardiac action potential.
Beta-adrenergic stimulation reverses the I Kr-I Ks dominant pattern during cardiac action potential.
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DOI：
10.1007/s00424-014-1465-7
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发表时间：
2014-11
影响因子：
4.5
通讯作者：
Chen-Izu, Ye
中科院分区：
文献类型：
--
作者：
Banyasz, Tamas;Jian, Zhong;Horvath, Balazs;Khabbaz, Shaden;Izu, Leighton T.;Chen-Izu, Ye
β-肾上腺素能刺激差异性地调节不同的K+通道，从而微调心脏动作电位（AP）复极。然而，目前尚不清楚β-肾上腺素能刺激如何改变同一细胞中IKs、IKr和IK 1电流的比例，这将改变单个K+电流对总复极储备的相对贡献。在这项研究中，我们使用了一个创新的AP钳顺序解剖技术，直接记录动态的IKs，IKr，IK 1电流在豚鼠心室肌细胞的AP在生理相关条件下。我们的数据提供了定量测量IKs，IKr，IK 1电流的大小和时间过程中在同一个细胞下，其自身的稳态AP，在生理环境中，并保存Ca 2+稳态。我们发现，异丙肾上腺素治疗显著增加IKs，中度增加IK 1，但略有下降IKr的剂量依赖性方式。对照组钾电流的优势模式为IKr> IK 1>IKs，而β-肾上腺素能刺激后则变为IKr<IK 1 <IKs。系统测定了不同肾上腺素能状态下AP时IKs、IKr、IK 1对心脏复极的相对贡献。总之，β-肾上腺素能刺激通过以剂量依赖性方式改变不同K+电流的功率来微调心脏AP形态。这些知识对于设计抗心律失常药物策略以治疗暴露于各种交感神经紧张的心脏是重要的。
β-adrenergic stimulation differentially modulates different K+ channels and thus fine-tunes cardiac action potential (AP) repolarization. However, it remains unclear how the proportion of IKs, IKr, and IK1 current in the same cell would be altered by β-adrenergic stimulation, which would change the relative contribution of individual K+ current to the total repolarization reserve. In this study we used an innovative AP-clamp Sequential Dissection technique to directly record the dynamic –IKs, IKr, IK1– currents during the AP in guinea pig ventricular myocytes under physiologically relevant conditions. Our data provide quantitative measures of the magnitude and time course of IKs, IKr, IK1 currents in the same cell under its own steady-state AP, in a physiological milieu, and with preserved Ca2+ homeostasis. We found that isoproterenol treatment significantly enhanced IKs, moderately increased IK1, but slightly decreased IKr in a dose-dependent manner. The dominance pattern of the K+ currents was IKr>IK1>IKs at the control condition, but reversed to IKr<IK1<IKs following β-adrenergic stimulation. We systematically determined the changes in the relative contribution of IKs, IKr, IK1 to cardiac repolarization during AP at different adrenergic states. In conclusion, the β-adrenergic stimulation fine-tunes the cardiac AP morphology by shifting the power of different K+ currents in a dose-dependent manner. This Knowledge is important for designing anti-arrhythmic drug strategies to treat the hearts exposed to various sympathetic tones.
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影响因子：
5
作者：
Grandi, Eleonora;Pasqualini, Francesco S.;Severi, Stefano
通讯作者：
Severi, Stefano
DOI：
10.1073/pnas.93.12.5819
发表时间：
1996-06-11
影响因子：
11.1
作者：
Wischmeyer, E;Karschin, A
通讯作者：
Karschin, A
影响因子：
5
作者：
Grimm M;Brown JH
通讯作者：
Brown JH
影响因子：
56.9
作者：
Marx, SO;Kurokawa, J;Kass, RS
通讯作者：
Kass, RS
影响因子：
20.1
作者：
SANGUINETTI, MC;JURKIEWICZ, NK;SIEGL, PKS
通讯作者：
SIEGL, PKS