January 1, 2017Circulation JournalOpen Access

Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy

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Why the study?

Does the SCN5A-D1275N mutation alter sodium channel function and NaV1.5 protein expression in patient-derived hiPSC-CMs?

Population

Human-induced pluripotent stem cell-derived cardiomyocytes generated from a 24-year-old Japanese female…

Comparison

SCN5A-D1275N mutation vs Wild-type SCN5A channels and control hiPSC-CMs

Design

Preclinical

Authors

MHMamoru HayanoKansai Electric Power Hospital TMTakeru MakiyamaKyoto University TKTsukasa KamakuraElectrophysiology

Discussion

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Implication

D1275N hiPSC model implicates proteasomal NaV1.5 degradation; hypothesis-generating for variant-specific therapies, should not yet change practice.

Structured PICO

Does the SCN5A-D1275N mutation alter sodium channel function and NaV1.5 protein expression in patient-derived hiPSC-CMs?

Population

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from a 24-year-old Japanese female patient with sinus node dysfunction and AV block carrying the heterozygous SCN5A-D1275N mutation, and control hiPSC-CMs from a healthy individual. Also human embryonic kidney (HEK) 293 cells expressing SCN5A-WT or -D1275N channels.

Intervention

SCN5A-D1275N mutation (and in vitro treatment with proteasome inhibitor MG132)

Comparator

Wild-type (WT) SCN5A channels and control hiPSC-CMs

Outcome

Electrophysiological properties (sodium current density, maximum sodium conductance, action potential parameters) and NaV1.5 protein expressionsurrogate

The SCN5A-D1275N mutation causes diminished sodium currents due to reduced NaV1.5 protein levels via proteasomal degradation, as demonstrated in a patient-derived hiPSC model.

Cite This Study

Hayano et al. (2017) studied this question.

synapsesocial.com/papers/6a207988cbc595e19031811a https://doi.org/10.1253/circj.cj-17-0064

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Implication

D1275N hiPSC model implicates proteasomal NaV1.5 degradation; hypothesis-generating for variant-specific therapies, should not yet change practice.

Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy

Discussion

Member takes

Implication

Structured PICO

Cite This Study

Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy

Discussion

Member takes

Implication

Structured PICO

Cite This Study

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