Abstract
Late sodium current has long been linked to dysrhythmia and contractile malfunction in the heart. Despite the increasing body of accumulating information on the subject, our understanding of its role in normal or pathologic states is not complete. Even though the role of late sodium current in shaping action potential under physiologic circumstances is debated, it’s unquestioned role in arrhythmogenesis keeps it in the focus of research. Transgenic mouse models and isoform-specific pharmacological tools have proved useful in understanding the mechanism of late sodium current in health and disease. This review will outline the mechanism and function of cardiac late sodium current with special focus on the recent advances of the area.
Highlights
Going? Pharmaceuticals 2022, 15, 231.The late component of cardiac sodium current has been the subject of extensive research since firstly described
Since mutations of neuronal sodium channels are known to facilitate resurgent current and expression of neuronal voltage gated sodium channels (VGSC) is demonstrated in cardiac myocytes, the resurgent current may potentially contribute to late sodium current and arrhythmogenesis
While considerable species differences are reported on channel gating, it seems that the overall effect of CaMKIIδC is increasing the magnitude of late sodium current in every model
Summary
One of the major obstacles in the late sodium current research is the tiny magnitude of the current. Especially in the presence of the huge transient phase, is a major challenge with the currently available experimental armory. Another limiting factor for progress is the limited availability of specific late sodium current inhibitors. Transgenic models [30] in order amplify the current magnitude These models offer increased methodical reliability in electrophysiological measurements but do not necessarily mirror the physiologic conditions. Pharmaceuticals 2022, 15, 231 outline our current understanding on the function of cardiac late sodium current in health and disease, with special emphasis on the last year’s development. The aim of this review is to report and discuss the major and most recent works that help to understand the precise function of this current in the heart
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