Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison

Frontiers in Pharmacology
Gildas LoussouarnFlavien Charpentier

Abstract

Mutations in Nav1.4 and Nav1.5 α-subunits have been associated with muscular and cardiac channelopathies, respectively. Despite intense research on the structure and function of these channels, a lot of information is still missing to delineate the various physiological and pathophysiological processes underlying their activity at the molecular level. Nav1.4 and Nav1.5 sequences are similar, suggesting structural and functional homologies between the two orthologous channels. This also suggests that any characteristics described for one channel subunit may shed light on the properties of the counterpart channel subunit. In this review article, after a brief clinical description of the muscular and cardiac channelopathies related to Nav1.4 and Nav1.5 mutations, respectively, we compare the knowledge accumulated in different aspects of the expression and function of Nav1.4 and Nav1.5 α-subunits: the regulation of the two encoding genes (SCN4A and SCN5A), the associated/regulatory proteins and at last, the functional effect of the same missense mutations detected in Nav1.4 and Nav1.5. First, it appears that more is known on Nav1.5 expression and accessory proteins. Because of the high homologies of Nav1.5 binding sites and equival...Continue Reading

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Citations

Feb 27, 2020·Cellular and Molecular Neurobiology·Bo JinXiaofeng Yin
Mar 8, 2017·Pflügers Archiv : European journal of physiology·Karan R ChaddaChristopher L-H Huang
Apr 12, 2020·International Journal of Molecular Sciences·Chiung-Wei HuangMing-Jen Lee
Oct 29, 2020·Nature Reviews. Neurology·Matthew AlsaloumStephen G Waxman
Nov 5, 2020·International Journal of Molecular Sciences·Magdalena KowalskaAlicja Nowaczyk
Nov 5, 2019·Biochemical and Biophysical Research Communications·Svetlana I TarnovskayaDmitrij Frishman

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