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钾通道在胎儿向新生儿肺循环过渡中的作用。

Potassium Channels in the Transition from Fetal to the Neonatal Pulmonary Circulation.

机构信息

Ludwig Boltzmann Institute for Lung Vascular Research, Neue Stiftingtalstraße 6, 8010 Graz, Austria.

Experimental Anaesthesiology, Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Auenbruggerplatz 5, 8036 Graz, Austria.

出版信息

Int J Mol Sci. 2022 Apr 23;23(9):4681. doi: 10.3390/ijms23094681.

DOI:10.3390/ijms23094681
PMID:35563072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9106051/
Abstract

The transition from the fetal to the neonatal circulation includes dilatation of the pulmonary arteries (PA) and closure of the Ductus Arteriosus Botalli (DAB). The resting membrane potential and various potassium channel activities in smooth muscle cells (SMC) from fetal and neonatal PA and DAB obtained from the same species has not been systematically analyzed. The key issue addressed in this paper is how the resting membrane potential and the whole-cell potassium current (IK) change when PASMC or DABSMC are transitioned from hypoxia, reflecting the fetal state, to normoxia, reflecting the post-partal state. Patch-clamp measurements were employed to characterize whole-cell K channel activity in fetal and post-partal (newborn) PASMC and DABSMC. The main finding of this paper is that the SMC from both tissues use a similar set of K channels (voltage-dependent (Kv), calcium-sensitive (KCa), TASK-1 and probably also TASK-2 channels); however, their activity level depends on the cell type and the oxygen level. Furthermore, we provide the first evidence for pH-sensitive non-inactivating K current in newborn DABSMC and PASMC, suggesting physiologically relevant TASK-1 and TASK-2 channel activity, the latter particularly in the Ductus Arteriosus Botalli.

摘要

从胎儿循环向新生儿循环的转变包括肺动脉 (PA) 的扩张和 Botalli 动脉导管 (DAB) 的关闭。来自同一物种的胎儿和新生儿 PA 和 DAB 的平滑肌细胞 (SMC) 的静息膜电位和各种钾通道活性尚未得到系统分析。本文解决的关键问题是,当 PASMC 或 DABSMC 从反映胎儿状态的缺氧转变为反映产后状态的正常氧时,静息膜电位和全细胞钾电流 (IK) 如何变化。膜片钳测量用于表征胎儿和产后 (新生儿) PASMC 和 DABSMC 的全细胞 K 通道活性。本文的主要发现是,来自两种组织的 SMC 使用类似的一组 K 通道(电压依赖性 (Kv)、钙敏感性 (KCa)、TASK-1 通道,可能还有 TASK-2 通道);然而,它们的活性水平取决于细胞类型和氧气水平。此外,我们提供了新生儿 DABSMC 和 PASMC 中 pH 敏感非失活 K 电流的第一个证据,表明存在与生理相关的 TASK-1 和 TASK-2 通道活性,后者在 Botalli 动脉导管中尤为明显。

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本文引用的文献

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Potassium (K) channels in the pulmonary vasculature: Implications in pulmonary hypertension Physiological, pathophysiological and pharmacological regulation.肺血管中的钾 (K) 通道:在肺动脉高压中的意义 生理、病理生理和药理学调节。
Pharmacol Ther. 2021 Sep;225:107835. doi: 10.1016/j.pharmthera.2021.107835. Epub 2021 Mar 18.
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Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure.调控出生后动脉导管闭合的分子机制。
Int J Mol Sci. 2018 Jun 25;19(7):1861. doi: 10.3390/ijms19071861.
3
The role of pH-sensitive TASK channels in central respiratory chemoreception.
pH 敏感的 TASK 通道在中枢呼吸化学感受中的作用。
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Redox regulation of ion channels in the pulmonary circulation.肺循环中离子通道的氧化还原调节
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Perforated whole-cell patch-clamp recording.穿孔全细胞膜片钳记录
Methods Mol Biol. 2013;998:149-57. doi: 10.1007/978-1-62703-351-0_11.
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Src tyrosine kinase is crucial for potassium channel function in human pulmonary arteries.Src 酪氨酸激酶对于人肺血管钾通道功能至关重要。
Eur Respir J. 2013 Jan;41(1):85-95. doi: 10.1183/09031936.00211811. Epub 2012 Apr 20.
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Am J Respir Cell Mol Biol. 2012 Mar;46(3):372-9. doi: 10.1165/rcmb.2010-0428OC. Epub 2011 Oct 20.
9
Hypoxia. 4. Hypoxia and ion channel function.缺氧。4. 缺氧与离子通道功能。
Am J Physiol Cell Physiol. 2011 May;300(5):C951-67. doi: 10.1152/ajpcell.00512.2010. Epub 2010 Dec 22.
10
Regulation of the pulmonary circulation in the fetus and newborn.胎儿和新生儿肺循环的调节。
Physiol Rev. 2010 Oct;90(4):1291-335. doi: 10.1152/physrev.00032.2009.