生理学上,首先是Aria合同,接着是心室,这是正常血液循环的先决条件。房室顺序收缩的上述现象是由心房和心室之间的房室结(AVN)的电激励的典型缓慢传导引起的。然而,尚不清楚是什么控制了AVN内电激励的传导。这里,我们发现AVN起搏细胞(AVNPCs)具有完整的固有GABA能系统,在从心房到心室的电传导中起着关键作用。首先,随着在AVNPCs的表面膜下发现丰富的含GABA的囊泡,GABA能系统的关键元素,包括GABA代谢酶,GABA受体,和GABA转运蛋白,在AVNPC中被识别。第二,GABA在AVNPC中同步引发GABA门控电流,显着削弱了AVNPC的兴奋性。第三,GABA能系统的关键分子元件显着调节了AVN中电激发的电导率。第四,AVNPCs中GABAA受体缺乏加速房室传导,这损害了AVN对快速心室频率响应的保护潜力,增加对致命性室性心律失常的易感性,并降低心脏收缩功能。最后,针对GABA能系统的干预措施可有效预防房室传导阻滞的发生和发展。总之,AVNPCs中的内源性GABA能系统决定了AVN内电激发的缓慢传导,从而确保连续房室收缩。内源性GABA能系统有望成为心律失常的新型干预目标。
Physiologically, the atria contract first, followed by the ventricles, which is the prerequisite for normal blood circulation. The above phenomenon of atrioventricular sequential contraction results from the characteristically slow conduction of electrical excitation of the atrioventricular node (AVN) between the atria and the ventricles. However, it is not clear what controls the conduction of electrical excitation within AVNs. Here, we find that AVN pacemaker cells (AVNPCs) possess an intact intrinsic GABAergic system, which plays a key role in electrical conduction from the atria to the ventricles. First, along with the discovery of abundant GABA-containing vesicles under the surface membranes of AVNPCs, key elements of the GABAergic system, including GABA metabolic enzymes, GABA receptors, and GABA transporters, were identified in AVNPCs. Second, GABA synchronously elicited GABA-gated currents in AVNPCs, which significantly weakened the excitability of AVNPCs. Third, the key molecular elements of the GABAergic system markedly modulated the conductivity of electrical excitation in the AVN. Fourth, GABAA receptor deficiency in AVNPCs accelerated atrioventricular conduction, which impaired the AVN\'s protective potential against rapid ventricular frequency responses, increased susceptibility to lethal ventricular arrhythmias, and decreased the cardiac contractile function. Finally, interventions targeting the GABAergic system effectively prevented the occurrence and development of atrioventricular block. In summary, the endogenous GABAergic system in AVNPCs determines the slow conduction of electrical excitation within AVNs, thereby ensuring sequential atrioventricular contraction. The endogenous GABAergic system shows promise as a novel intervention target for cardiac arrhythmias.