Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes.
Ionic current changes underlying action potential repolarization responses to physiological pacing and adrenergic stimulation in adult rat ventricular myocytes.
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DOI：
10.14814/phy2.15766
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发表时间：
2023-07
影响因子：
2.5
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中科院分区：
文献类型：
--
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本研究旨在利用一种新的电生理学大鼠模型模拟心肌细胞起搏和肾上腺素能刺激时的心室反应，并研究动作电位(AP)调节下的离子通道反应。在对照组和肾上腺素能刺激条件下，模拟1~10 赫兹起搏，记录到峰值离子电流和AP复极至全复极的50%和90%(APD50-90)。用增量离子电流阻滞剂(L型钙电流、瞬时外向电流、慢延迟整流钾电流、快速延迟整流钾电流、内向整流钾电流)进一步模拟AP对运动反应的影响。模拟的APD50-90与实验结果非常相似。IKs(6%-101%)、Ikr(141%-1339%)和ICa(0%-15%)呈速率依赖性增加，Ito(11%-57%)和Ik1(1%-9%)减少。同时，肾上腺素能刺激引起除IK1外的所有电流的适度增加(23%-67%)。进一步分析表明，AP平台对Ito和Ica的调制最为敏感，而晚期复极对Ik1、Ica和Iks最为敏感，IKs的改变对晚期复极的影响最大(APD90延长35%-846%)。改良的利兹大鼠模型(MLR)能够准确地模拟生理应激状态下的AP。这项研究强调了ICA、Ito、Ik1和Iks在控制运动的电生理反应中的重要性。这项工作将有助于心脏功能障碍、心律失常和疾病的研究，尽管未来还需要进行生理学相关的实验研究和模型开发。
This study aimed to simulate ventricular responses to elevations in myocyte pacing and adrenergic stimulation using a novel electrophysiological rat model and investigate ion channel responses underlying action potential (AP) modulations. Peak ion currents and AP repolarization to 50% and 90% of full repolarization (APD50‐90) were recorded during simulations at 1–10 Hz pacing under control and adrenergic stimulation conditions. Further simulations were performed with incremental ion current block (L‐type calcium current, ICa; transient outward current, Ito; slow delayed rectifier potassium current, IKs; rapid delayed rectifier potassium current, IKr; inward rectifier potassium current, IK1) to identify current influence on AP response to exercise. Simulated APD50‐90 closely resembled experimental findings. Rate‐dependent increases in IKs (6%–101%), IKr (141%–1339%), and ICa (0%–15%) and reductions in Ito (11%–57%) and IK1 (1%–9%) were observed. Meanwhile, adrenergic stimulation triggered moderate increases in all currents (23%–67%) except IK1. Further analyses suggest AP plateau is most sensitive to modulations in Ito and ICa while late repolarization is most sensitive to IK1, ICa, and IKs, with alterations in IKs predominantly stimulating the greatest magnitude of influence on late repolarization (35%–846% APD90 prolongation). The modified Leeds rat model (mLR) is capable of accurately modeling APs during physiological stress. This study highlights the importance of ICa, Ito, IK1, and IKs in controlling electrophysiological responses to exercise. This work will benefit the study of cardiac dysfunction, arrythmia, and disease, though future physiologically relevant experimental studies and model development are required.
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