The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.
The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.
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DOI：
10.1085/jgp.202213193
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发表时间：
2022-12-05
影响因子：
3.8
通讯作者：
Proenza, Catherine
中科院分区：
文献类型：
--
作者：
Peters, Colin H.;Rickert, Christian;Morotti, Stefano;Grandi, Eleonora;Aronow, Kurt A.;Beam, Kurt G.;Proenza, Catherine
有趣电流（If）对心脏起搏至关重要。在这里，我们表明If对于心率的“战或逃”增加也至关重要，占小鼠窦房结肌细胞AP放电率增加的0.40%。交感神经系统战斗或逃跑反应的特征在于心率的快速增加，其由窦房结中起搏细胞的自发动作电位（AP）放电率的增加介导。交感神经元通过激活β肾上腺素能受体（β AR）和增加cAMP来刺激窦房肌细胞（SAM）。有趣电流（If）是SAM中cAMP敏感电流之一。然而，它对于起搏器活动至关重要，它在战或逃反应中的作用仍然存在争议。在这项研究中，我们使用AP波形分析，机器学习和动态钳实验在急性分离的SAM从小鼠定量定义AP波形的变化和作用，如果在战斗或飞行增加AP放电率。我们发现，虽然βAR刺激显著改变了几乎所有的AP波形参数，但放电频率的增加仅与一部分参数（舒张期持续时间、晚期AP持续时间和舒张期去极化率）的变化相关。动态钳夹注射If的β AR敏感成分，可使AP放电频率增加约41%，AP间期缩短约60%。因此，如果是一个重要的贡献者战斗或飞行增加心率。
The funny current (If) is critical for cardiac pacemaking. Here, we show that If is also essential for the fight-or-flight increase in heart rate, accounting for ∼40% of the increase in AP firing rate in mouse sinoatrial node myocytes. The sympathetic nervous system fight-or-flight response is characterized by a rapid increase in heart rate, which is mediated by an increase in the spontaneous action potential (AP) firing rate of pacemaker cells in the sinoatrial node. Sympathetic neurons stimulate sinoatrial myocytes (SAMs) by activating β adrenergic receptors (βARs) and increasing cAMP. The funny current (If) is among the cAMP-sensitive currents in SAMs. If is critical for pacemaker activity, however, its role in the fight-or-flight response remains controversial. In this study, we used AP waveform analysis, machine learning, and dynamic clamp experiments in acutely isolated SAMs from mice to quantitatively define the AP waveform changes and role of If in the fight-or-flight increase in AP firing rate. We found that while βAR stimulation significantly altered nearly all AP waveform parameters, the increase in firing rate was only correlated with changes in a subset of parameters (diastolic duration, late AP duration, and diastolic depolarization rate). Dynamic clamp injection of the βAR-sensitive component of If showed that it accounts for ∼41% of the fight-or-flight increase in AP firing rate and 60% of the decrease in the interval between APs. Thus, If is an essential contributor to the fight-or-flight increase in heart rate.
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影响因子：
20.1
作者：
Gao Z;Rasmussen TP;Li Y;Kutschke W;Koval OM;Wu Y;Wu Y;Hall DD;Joiner ML;Wu XQ;Swaminathan PD;Purohit A;Zimmerman K;Weiss RM;Philipson KD;Song LS;Hund TJ;Anderson ME
通讯作者：
Anderson ME
影响因子：
5
作者：
Bucchi, Annalisa;BaruSCotti, Mad;DiFrancesco, Dario
通讯作者：
DiFrancesco, Dario
DOI：
10.33594/000000119
发表时间：
2019-01-01
期刊：
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子：
--
作者：
Haechl, Nicholas;Ebner, Janine;Koenig, Xaver
通讯作者：
Koenig, Xaver
影响因子：
11.4
作者：
Harzheim, Dagmar;Pfeiffer, K. Holger;Seifert, Reinhard
通讯作者：
Seifert, Reinhard
影响因子：
11.4
作者：
Herrmann, Stefan;Stieber, Juliane;Ludwig, Andreas
通讯作者：
Ludwig, Andreas