4.6 Article

Effects of Allicin on Late Sodium Current Caused by ΔKPQ-SCN5A Mutation in HEK293 Cells

Journal

FRONTIERS IN PHYSIOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2021.636485

Keywords

Allitridum; Δ KPQ-SCN5A mutation; HEK293 cells; late sodium current; LQT3

Categories

Funding

  1. National Natural Science Foundation of China [82070341, 81870249, 82070328]
  2. Natural Science Foundation of Fujian Province [2015J01370, 2019J01189]
  3. Key Innovation Project of Fujian Province Health Department [2017-CX-6]
  4. Fujian Provincial Hospital [2017LHJJ02, 2020HSJJ11]

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The study revealed that Allicin reduced the late sodium current of Delta KPQ-SCN5A, possibly by increasing channel steady-state inactivation (SSI) and intermediate-state inactivation (ISI), thereby reducing the window current.
Aim The aim was to study the effect of Allitridum (Allicin) on the heterologous expression of the late sodium current on the Delta KPQ-SCN5A mutations in HEK293 cells, with a view to screening new drugs for the treatment of long QT syndrome type 3 (LQT3). Methods and Results The Delta KPQ-SCN5A plasmid was transiently transferred into HEK293 cells by liposome technology and administered by extracellular perfusion, and the sodium current was recorded by whole-cell patch-clamp technology. Application of Allicin 30 mu M reduced the late sodium current (I-Na,I-L) of the Nav1.5 channel current encoded by Delta KPQ-SCN5A from 1.92 +/- 0.12 to 0.65 +/- 0.03 pA/pF (P < 0.01, n = 15), which resulted in the decrease of I-Na,I-L/I-Na,I-P (from 0.94% +/- 0.04% to 0.32% +/- 0.02%). Furthermore, treatment with Allicin could move the steady-state inactivation of the channel to a more negative direction, resulting in an increase in channel inactivation at the same voltage, which reduced the increase in the window current and further increased the inactivation of the channel intermediate state. However, it had no effect on channel steady-state activation (SSA), inactivation mechanics, and recovery dynamics after inactivation. What's more, the Nav1.5 channel protein levels of membrane in the Delta KPQ-SCN5A mutation were enhanced from 0.49% +/- 0.04% to 0.76% +/- 0.02% with the effect of 30 mM Allicin, close to 0.89% +/- 0.02% of the WT. Conclusion Allicin reduced the late sodium current of Delta KPQ-SCN5A, whose mechanism may be related to the increase of channel steady-state inactivation (SSI) and intermediate-state inactivation (ISI) by the drug, thus reducing the window current.

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