Molecular expression of multiple Nav1.5 splice variants in the frontal lobe of the human brain

Voltage-gated sodium channels serve an essential role in the initiation and propagation of action potentials for central neurons. Previous studies have demonstrated that two novel variants of Nav1.5, designated Nav1.5e and Nav1.5f, were expressed in the human brain cortex. To date, nine distinct sod...

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Bibliographic Details
Published in:International journal of molecular medicine 2018-02, Vol.41 (2), p.915-923
Main Authors: Wang, Jun, Ou, Shao-Wu, Zhang, Zhi-Yong, Qiu, Bo, Wang, Yun-Jie
Format: Article
Language:English
Subjects:
Brain
Cloning
Deoxyribonucleic acid
DNA
Enzymes
Epilepsy
Gene expression
Genetic aspects
Genetic variation
Health aspects
Mortality
Mutation
Neural circuitry
Sodium
Sodium channels
Studies
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Summary:Voltage-gated sodium channels serve an essential role in the initiation and propagation of action potentials for central neurons. Previous studies have demonstrated that two novel variants of Nav1.5, designated Nav1.5e and Nav1.5f, were expressed in the human brain cortex. To date, nine distinct sodium channel isoforms of Nav1.5 have been identified. In the present study, the expression of Nav1.5 splice variants in the frontal lobe of the human brain cortex was systematically investigated. The results demonstrated that wild Nav1.5 and its splice variants, Nav1.5c and Nav1.5e, were expressed in the frontal lobe of the human brain cortex. Nav1.5a, Nav1.5b and Nav1.5d splice variants were not detected. However, the expression level of different Nav1.5 variants was revealed to vary. The expression ratio of wild Nav1.5 vs. Nav1.5c and Nav1.5e was approximately 5:1 and 1:5, respectively. Immunochemistry results revealed that Nav1.5 immunoreactivity was predominantly in neuronal cell bodies and processes, including axons and dendrites, whereas little immunoreactivity was detected in the glial components. These results revealed that a minimum of four Nav1.5 splice variants are expressed in the frontal lobe of the human brain cortex. This indicates that the previously reported tetrodotoxin-resistant sodium current was a compound product of different Nav1.5 variants. The present study revealed that Nav1.5 channels have a more abundant expression in the human brain than previously considered. It also provided further insight into the complexity and functional significance of Nav1.5 channels in human brain neurons.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2017.3286