Diadenosine tetraphosphate (Ap4A) belongs to a group of endogenous purine compounds that have recently been considered as new neurotransmitters or cotransmitters in the autonomic nervous system. It has been shown that Ap4A affects electrophysiology of a pacemaker and working myocardium and modulates adrenergic control of the heart in adult mammals. Nevertheless, the physiological role of Ap4A in the regulation of bioelectric properties in the pulmonary vein (PV) myocardium has not yet been investigated. It is well known that myocardial tissue in the wall of the PV acts as source of the ectopic proarrhythmic activity that underlies supraventricular arrhythmias like atrial fibrillation. The aim of the present study was to elucidate the effects Ap4A on bioelectrical properties and proarrhythmic ectopy in PVs in adult rats and at early postnatal ontogenesis. Thus, the resting potentials and the electrically evoked and spontaneous action potentials were recorded with the use of the standard microelectrode technique in multicellular isolated PV specimens from male Wistar rats at postnatal days 1-, 7-, 14-, and 21- and also from 60-day-old animals, which were considered as mature. The application of Ap4A caused significant reduction of action potential duration in PV specimens from rats of all ages. Ap4A also caused significant resting membrane potential hyperpolar-ization in quiescent PVs specimens from 14-, 21-, and 60-day-old rats. In addition, Ap4A caused complete and significant suppression of ectopic automaticity caused by preliminary noradrenaline administration in PV from 21- and 60-day-old rats, but Ap4A was unable to alter spontaneous intrinsic activity in PV from neo-nate (1-day-old) rats. The Ap4A-caused attenuation of noradrenaline-induced ectopy in PV was accompanied by substantial resting membrane potential hyperpolarization in all cases. Our results allow suggesting that the release of Ap4A as a cotransmitter from autonomic nerve endings can reduce proarrhythmic ectopy caused by sympathetic stimulation of the PV myocardium in vivo.

中文翻译：

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细胞外腺苷四磷酸可抑制成年大鼠肺静脉心肌组织的异位心律失常

四磷酸腺苷（Ap4A）属于一组内源性嘌呤化合物，最近被认为是植物神经系统中的新神经递质或共递质。已显示，Ap4A影响起搏器和正常工作的心肌的电生理，并调节成年哺乳动物心脏的肾上腺素能控制。然而，尚未研究Ap4A在调节肺静脉（PV）心肌的生物电特性中的生理作用。众所周知，PV壁中的心肌组织是异位心律失常活动的来源，而异位心律失常活动是诸如心房纤颤之类的室上性心律失常的基础。本研究的目的是阐明Ap4A对成年大鼠和产后早期成体中PVs的生物电特性和心律失常的影响。因此，使用标准的微电极技术，在雄性Wistar大鼠出生后第1、7、14、21天以及之后的多细胞分离的PV标本中记录了静息电位，电诱发的和自发的动作电位。 60天大的动物，被认为是成熟的。Ap4A的使用大大降低了所有年龄段大鼠的PV样本中动作电位的持续时间。Ap4A还导致14、21和60天龄大鼠的静态PV样品中明显的静止膜电位超极化。此外，Ap4A导致完全和显着抑制初次去甲肾上腺素对21日龄和60日龄大鼠的PV引起的异位自动化，但Ap4A不能改变新生1天龄大鼠PV的自发内在活性。 。在所有情况下，Ap4A引起去甲肾上腺素诱发的PV异位的衰减都伴随着大量的静息膜电位超极化。我们的结果表明，从自主神经末梢释放作为辅助递质的Ap4A可以减少体内对PV心肌的交感刺激引起的心律失常。在所有情况下，Ap4A引起去甲肾上腺素诱发的PV异位的衰减都伴随着大量的静息膜电位超极化。我们的结果表明，从自主神经末梢释放作为辅助递质的Ap4A可以减少体内对PV心肌的交感刺激引起的心律失常。在所有情况下，Ap4A引起去甲肾上腺素诱发的PV异位的衰减都伴随着大量的静息膜电位超极化。我们的结果表明，从自主神经末梢释放作为辅助递质的Ap4A可以减少体内对PV心肌的交感刺激引起的心律失常。