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伴有GATA4表达的α1-肾上腺素能受体与大鼠房间隔的致心律失常传导和自律性有关。

α1-adrenergic receptors accompanied by GATA4 expression are related to proarrhythmic conduction and automaticity in rat interatrial septum.

作者信息

Pustovit Ksenia B, Samoilova Daria V, Abramochkin Denis V, Filatova Tatiana S, Kuzmin Vladislav S

机构信息

Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia.

N. N. Blokhin National Medical Research Centre of Oncology, Kashirskoye sh., 24, Moscow, Russia.

出版信息

J Physiol Biochem. 2022 Nov;78(4):793-805. doi: 10.1007/s13105-022-00902-8. Epub 2022 Jul 8.

Abstract

The development of interatrial septum (IAS) is a complicated process, which continues during postnatal life. The hypertrophic signals in developing heart are mediated among others by α-adrenergic pathways. These facts suggest the presence of specific electrophysiological features in developing IAS. This study was aimed to investigate the electrical activity in the tissue preparations of IAS from rat heart in normal conditions and under stimulation of adrenoreceptors. Intracellular recording of electrical activity revealed less negative level of resting membrane potential in IAS if compared to myocardium of left atrium. In normal conditions, non-paced IAS preparations were quiescent, but noradrenaline (10 M) and phenylephrine (10 M) induced spontaneous action potentials, which could be abolished by α1-blocker prazosin (10 M), but not β1-blocker atenolol (10 M). Optical mapping showed drastic phenylephrine-induced slowing of conduction in adult rat IAS. The α1-dependent ectopic automaticity of IAS myocardium might be explained by immunohistochemical data indicating the presence of transcription factor GATA4 and abundant α1A-adrenoreceptors in myocytes from adult rat IAS. An elevated sensitivity to adrenergic stimulation due to involvement of α1-adrenergic pathways may underlie increased proarrhythmic potential of adult IAS at least in rats.

摘要

房间隔(IAS)的发育是一个复杂的过程,在出生后仍在继续。发育中心脏的肥厚信号部分由α-肾上腺素能通路介导。这些事实表明发育中的IAS存在特定的电生理特征。本研究旨在研究正常条件下以及在肾上腺素能受体刺激下大鼠心脏IAS组织标本中的电活动。电活动的细胞内记录显示,与左心房心肌相比,IAS的静息膜电位负值较小。在正常条件下,未起搏的IAS标本是静止的,但去甲肾上腺素(10 μM)和苯肾上腺素(10 μM)可诱导自发动作电位,α1受体阻滞剂哌唑嗪(10 μM)可消除这些电位,但β1受体阻滞剂阿替洛尔(10 μM)则不能。光学标测显示苯肾上腺素可使成年大鼠IAS的传导显著减慢。成年大鼠IAS心肌细胞中存在转录因子GATA4和丰富的α1A-肾上腺素能受体,免疫组化数据或许可以解释IAS心肌的α1依赖性异位自律性。至少在大鼠中,由于α1-肾上腺素能通路的参与,对肾上腺素能刺激的敏感性升高可能是成年IAS心律失常潜在风险增加的原因。

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