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Multiple Nav1.5 isoforms are functionally expressed in the brain and present distinct expression patterns compared

Jun Wang1, Shao-Wu Ou2, Yun-Fei Bai3

  • 1Department of Neurosurgery, Beijing Sanbo Brain Hospital of Capital Medical University, Beijing 100093, P.R. China.

Molecular Medicine Reports
|June 1, 2017
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Summary

Neonatal and adult Nav1.5 splice variants are expressed in rat brain neurons. Electrophysiological analysis confirms functional Nav1.5 expression in the brain, with distinct developmental expression ratios compared to the heart.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Electrophysiology

Background:

  • Voltage-gated sodium channel (Nav) 1.5 splice variants are known to be expressed in brain tissue.
  • While nine Nav1.5 isoforms have been identified, the presence of additional variants in brain neurons requires further investigation.

Purpose of the Study:

  • To systematically investigate the expression of various Nav1.5 splice variants in rat brain tissue.
  • To characterize the associated electrophysiological properties of these Nav1.5 variants in the rat brain.

Main Methods:

  • Biochemical analyses were employed to study Nav1.5 splice variant expression.
  • Whole-cell patch clamp recordings were utilized for electrophysiological characterization.
  • Immunohistochemistry was performed to determine the cellular localization of Nav1.5.

Main Results:

  • Adult, neonatal Nav1.5, Nav1.5a, and Nav1.5f isoforms were detected in adult rat brain.
  • The ratio of neonatal to adult Nav1.5 expression decreased with age in the brain, differing from cardiac tissue.
  • Nav1.5 immunoreactivity was primarily in neuronal cell bodies and processes, with minimal glial presence.
  • Electrophysiological analysis confirmed a tetrodotoxin (TTX)-resistant Na current in rat brain slices, functional at specific voltage potentials.

Conclusions:

  • Both neonatal and adult Nav1.5 splice variants are expressed in the rat brain.
  • Electrophysiological data confirm the functional expression of Nav1.5 within brain neurons.