Curcumin, a Dietary Natural Supplement, Prolongs the Action Potential Duration of KCNE1-D85N Induced Pluripotent Stem Cell-Derived Cardiomyocytes

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Curcumin, a Dietary Natural Supplement, Prolongs the Action Potential Duration of KCNE1-D85N Induced Pluripotent Stem Cell-Derived Cardiomyocytes

• Katherine Martinez ^∗
• Annabel Smith ^∗
• Dan Ye, MD
• Wei Zhou, MD
• David J. Tester, BS
• Michael J. Ackerman, MD, PhD
• Show footnotes

Published:December 27, 2022DOI:https://doi.org/10.1016/j.hrthm.2022.12.034

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Abstract

BACKGROUND

Curcumin, a polyphenolic dietary natural compound and active ingredient in turmeric, exerts antioxidant, anti-inflammatory, antidiabetic, anti-cancer, and antiarrhythmic properties. KCNE1-D85N, present in approximately 1% of Caucasians, is a common, potentially pro-arrhythmic variant that predisposes individuals to drug-induced QT prolongation under certain conditions.

OBJECTIVE

To test the hypothesize that curcumin might cause action potential duration (APD) prolongation in KCNE1-D85N derived human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

METHODS

Gene-edited/variant-corrected isogenic control and patient-specific, KCNE1-D85N containing iPSC-CMs were generated previously. Fluovolt, multielectrode array (MEA), and whole-cell patch clamp were performed to measure APD without and with 4-hour incubation of 10 nM Curcumin.

RESULTS

KCNE1-D85N derived iPSC-CMs demonstrated significant APD prolongation with treatment of 10 nM curcumin. Using Fluovolt, the APD90 was 578 ± 7 ms (n=39) at baseline and was prolonged to 658 ± 13 ms (n=35, p<0.0001) with curcumin incubation. Using MEA, the APD90 at baseline was 237 ± 6 ms (n=24), compared to 280 ± 6 ms (n=12, p=0.0002) with curcumin incubation. Whole-cell patch clamp confirmed these results with the APD90 of 544 ± 37 ms at baseline and 664 ± 40 ms (p < 0.005) with treatment of curcumin. However, the APD from isogenic control iPSC-CMs remained unchanged with curcumin treatment.

CONCLUSIONS

This study provides pharmacological and functional evidence to suggest that curcumin, a dietary natural supplement, might cause APD prolongation in the patients with common, potentially pro-arrhythmic functional variants such as KCNE1-D85N. Whether this supplement is potentially dangerous for the Caucasian sub-population who possess this variant warrants further investigation.