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Original Article

Korean J Physiol Pharmacol 2024; 28(4): 335-344

Published online July 1, 2024

Copyright © Korean J Physiol Pharmacol.

The NADPH oxidase inhibitor diphenyleneiodonium suppresses Ca2+ signaling and contraction in rat cardiac myocytes

Qui Anh Le1,#, Tran Nguyet Trinh1,#, Phuong Kim Luong1, Vu Thi Van Anh1, Ha Nam Tran1, Joon-Chul Kim1,2, and Sun-Hee Woo1,*

1College of Pharmacy, Chungnam National University, Daejeon 34134, 2Nexel Co. Ltd., Seoul 07802, Korea

Correspondence to:Sun-Hee Woo

#These authors contributed equally to this work.

Received: April 8, 2024; Revised: April 14, 2024; Accepted: April 15, 2024


Diphenyleneiodonium (DPI) has been widely used as an inhibitor of NADPH oxidase (Nox) to discover its function in cardiac myocytes under various stimuli. However, the effects of DPI itself on Ca2+ signaling and contraction in cardiac myocytes under control conditions have not been understood. We investigated the effects of DPI on contraction and Ca2+ signaling and their underlying mechanisms using video edge detection, confocal imaging, and whole-cell patch clamp technique in isolated rat cardiac myocytes. Application of DPI suppressed cell shortenings in a concentration-dependent manner (IC50 of ≅0.17 µM) with a maximal inhibition of ~70% at ~100 µM. DPI decreased the magnitude of Ca2+ transient and sarcoplasmic reticulum Ca2+ content by 20%–30% at 3 µM that is usually used to remove the Nox activity, with no effect on fractional release. There was no significant change in the half-decay time of Ca2+ transients by DPI. The L-type Ca2+ current (ICa) was decreased concentration-dependently by DPI (IC50 of ≅40.3 µM) with ≅13.1%-inhibition at 3 µM. The frequency of Ca2+ sparks was reduced by 3 µM DPI (by ~25%), which was resistant to a brief removal of external Ca2+ and Na+. Mitochondrial superoxide level was reduced by DPI at 3–100 µM. Our data suggest that DPI may suppress L-type Ca2+ channel and RyR, thereby attenuating Ca2+-induced Ca2+ release and contractility in cardiac myocytes, and that such DPI effects may be related to mitochondrial metabolic suppression.

Keywords: Cardiac myocytes, Ca2+ release, Contraction, Diphenyleneiodonium, L-type Ca2+ current