The Journal of Physiological Sciences

, Volume 69, Issue 6, pp 837–849 | Cite as

Cardiac Na+/Ca2+ exchange stimulators among cardioprotective drugs

  • Yasuhide WatanabeEmail author


We previously reviewed our study of the pharmacological properties of cardiac Na+/Ca2+ exchange (NCX1) inhibitors among cardioprotective drugs, such as amiodarone, bepridil, dronedarone, cibenzoline, azimilide, aprindine, and benzyl-oxyphenyl derivatives (Watanabe et al. in J Pharmacol Sci 102:7–16, 2006). Since then we have continued our studies further and found that some cardioprotective drugs are NCX1 stimulators. Cardiac Na+/Ca2+ exchange current (INCX1) was stimulated by nicorandil (a hybrid ATP-sensitive K+ channel opener), pinacidil (a non-selective ATP-sensitive K+ channel opener), flecainide (an antiarrhythmic drug), and sodium nitroprusside (SNP) (an NO donor). Sildenafil (a phosphodiesterase-5 inhibitor) further increased the pinacidil-induced augmentation of INCX1. In paper, here I review the NCX stimulants that enhance NCX function among the cardioprotective agents we examined such as nicorandil, pinacidil, SNP, sildenafil and flecainide, in addition to atrial natriuretic (ANP) and dofetilide, which were reported by other investigators.


Cardiac Na+/Ca2+ exchanger (NCX1) Cardiac Na+/Ca2+ exchange current (INCX1NCX1 stimulator Patch-clamp method Cardioprotective drug 



I thank Dr. Junko Kimura for helpful and critical comments on the manuscript. This study was supported by Grants-in-Aid for Scientific Research (17K11047) from the Japan Society for Promotion of Science.

Compliance with ethical standards

Conflict of interest

The author of this manuscript has no conflict of interest to declare.


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© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pharmacological Science, Department of Health ScienceHamamatsu University School of MedicineHamamatsuJapan

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