New Variants of Nav1.5/SCN5A Encode Na⁺ Channels in the Brain

Abstract

Exon6A of Nav1.5/SCN5A was first found in the cloning of Nav1.5 from the human neuroblastoma cell line NB-1 (Ou et al., ), but its expression in brain and non-brain tissue had not been identified. In this study, we have further investigated this new exon and compared it with exon6 of Nav1.5/SCN5A. Reverse transcription-polymerase chain reaction (RT-PCR) and sequence analysis both confirmed that it is exon6A that encodes Nav1.5 in brain tissue, and it is exon6 that encodes Nav1.5 in non-brain tissue. The expression of exon6A in different parts of the brain is different, with expression levels in the order of hippocampus > cerebral cortex > brain stem > cerebellum. Different expression levels of exon6 in different tissues of Wistar rats were also found. These results suggest that exon6A is unique in encoding the Nav1.5 channels in the central nervous system. In addition, novel alternative splicing of Nav1.5/SCN5A, lacking exon24, was first found in our study. This alternative splicing was also found in other tissues, such as heart, lung and testis. However, the ratio of the two variants changed differently in different types of tissues in developing rats. These results suggest that Nav1.5/SCN5A has a newly identified alternative splicing, and the Nav1.5 channels in the brain are encoded by new variants of Nav1.5/SCN5A.

Keywords:

• Alternative splicing
• Brain
• Exon6
• Exon6A
• Exon24
• Nav1.5/
• SCN5A

Abbreviations:

• a.a. amino acid
• hB: cDNA encoding the α-subunit of Nav1.5 in human brain tissue
• hH1: cDNA encoding the α-subunit of Nav1.5 in human heart tissue
• hNBR1: cDNA encoding the α-subunit of Nav1.5 in human neuroblastoma cells
• RT-PCR: reverse transcription-polymerase chain reaction
• TTX-R: tetrodotoxin-resistant
• TTX: tetrodotoxin