A zebrafish model of nondystrophic myotonia with sodium channelopathy

Tai Seung Nam, Jun Zhang, Gopalakrishnan Chandrasekaran, In Young Jeong, Wenting Li, So Hyun Lee, Kyung Wook Kang, Jin Soo Maeng, Hyuno Kang, Hee Young Shin, Hae Chul Park, Sohee Kim, Seok Yong Choi, Myeong Kyu Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Nondystrophic myotonias are disorders of Na+ (Nav1.4 or SCN4A) and Cl (CLCN1) channels in skeletal muscles, and frequently show phenotype heterogeneity. The molecular mechanism underlying their pathophysiology and phenotype heterogeneity remains unclear. As zebrafish models have been recently exploited for studies of the pathophysiology and phenotype heterogeneity of various human genetic diseases, a zebrafish model may be useful for delineating nondystrophic myotonias. Here, we generated transgenic zebrafish expressing a human mutant allele of SCN4A, referred to as Tg(mylpfa:N440K), and needle electromyography revealed increased number of myotonic discharges and positive sharp waves in the muscles of Tg(mylpfa:N440K) than in controls. In addition, forced exercise test at a water temperature of 24 °C showed a decrease in the distance moved, time spent in and number of visits to the zone with stronger swimming resistance. Finally, a forced exercise test at a water temperature of 18 °C exhibited a higher number of dive-bombing periods and drifting-down behavior than in controls. These findings indicate that Tg(mylpfa:N440K) is a good vertebrate model of exercise- and cold-induced human nondystrophic myotonias. This zebrafish model may contribute to provide insight into the pathophysiology of myotonia in sodium channelopathy and could be used to explore a new therapeutic avenue.

Original languageEnglish
Article number134579
JournalNeuroscience Letters
Volume714
DOIs
Publication statusPublished - 2020 Jan 1

Keywords

  • Hyperkalemic periodic paralysis
  • Myotonia
  • Paramyotonia congenita
  • Sodium channel
  • Zebrafish

ASJC Scopus subject areas

  • Neuroscience(all)

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