Zaitsev Alexey V, Warren Mark
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, United States.
Front Physiol. 2020 Feb 18;11:86. doi: 10.3389/fphys.2020.00086. eCollection 2020.
The traditional view of ventricular excitation and conduction is an all-or-nothing response mediated by a regenerative activation of the inward sodium channel, which gives rise to an essentially conduction velocity (CV). However, whereas there is no obvious biological need to tune-up ventricular conduction, the principal molecular components determining CV, such as sodium channels, inward-rectifier potassium channels, and gap junctional channels, are known targets of the "stress" protein kinases PKA and calcium/calmodulin dependent protein kinase II (CaMKII), and are thus by signal pathways converging on these kinases. In this mini-review we will expose deficiencies and controversies in our current understanding of how ventricular conduction is regulated by stress kinases, with a special focus on the chamber-specific dimension in this regulation. In particular, we will highlight an odd property of cardiac physiology: uniform CV in ventricles requires co-existence of mutually opposing gradients in cardiac excitability and stress kinase function. While the biological advantage of this peculiar feature remains obscure, it is important to recognize the clinical implications of this phenomenon pertinent to inherited or acquired conduction diseases and therapeutic interventions modulating activity of PKA or CaMKII.
传统观点认为，心室兴奋和传导是由内向钠通道的再生激活介导的全或无反应，这产生了基本的传导速度（CV）。然而，虽然没有明显的生物学需求来调节心室传导，但决定CV的主要分子成分，如钠通道、内向整流钾通道和缝隙连接通道，是“应激”蛋白激酶PKA和钙/钙调蛋白依赖性蛋白激酶II（CaMKII）的已知靶点，因此受到汇聚于这些激酶的信号通路的影响。在这篇小型综述中，我们将揭示目前我们对应激激酶如何调节心室传导的理解中的不足和争议，特别关注这种调节中的腔室特异性维度。特别是，我们将强调心脏生理学的一个奇特特性：心室中均匀的CV需要心脏兴奋性和应激激酶功能中相互对立的梯度共存。虽然这一独特特征的生物学优势仍不清楚，但认识到这一现象与遗传性或获得性传导疾病以及调节PKA或CaMKII活性的治疗干预相关的临床意义很重要。
