Korean J Physiol Pharmacol.  2016 Jan;20(1):119-127. 10.4196/kjpp.2016.20.1.119.

Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization

Affiliations
  • 1Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon 34114, Korea. idkks@kitox.re.kr
  • 2Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sjoonkim@snu.ac.kr
  • 3Human and Environmental Toxicology Program, University of Science and Technology, Daejeon 34113, Korea.

Abstract

Dihydropyridine (DHP) calcium channel blockers (CCBs) have been widely used to treat of several cardiovascular diseases. An excessive shortening of action potential duration (APD) due to the reduction of Ca2+ channel current (I(Ca)) might increase the risk of arrhythmia. In this study we investigated the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on the cardiac APD in rabbit Purkinje fibers, voltage-gated K+ channel currents (I(Kr), I(Ks)) and voltage-gated Na+ channel current (I(Na)). The concentration-dependent inhibition of Ca2+ channel currents (I(Ca)) was examined in rat cardiomyocytes; these CCBs have similar potency on I(Ca) channel blocking with IC50 (the half-maximum inhibiting concentration) values of 0.142, 0.229, and 0.227 nM on NIC, ISR, and AML, respectively. However, ISR shortened both APD50 and APD90 already at 1 microM whereas NIC and AML shortened APD50 but not APD90 up to 30 microM. According to ion channel studies, NIC and AML concentration-dependently inhibited I(Kr) and I(Ks) while ISR had only partial inhibitory effects (<50% at 30 microM). Inhibition of I(Na) was similarly observed in the three CCBs. Since the I(Kr) and I(Ks) mainly contribute to cardiac repolarization, their inhibition by NIC and AML could compensate for the AP shortening effects due to the block of I(Ca).

Keyword

Antihypertensives; Cardiac action potentials; Cardiac repolarization; Dihydropyridine calcium channel blockers; Ion channels
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