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Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization

Hyang-Ae Lee1, Sung-Ae Hyun2, Sung-Gurl Park2

  • 1Next-generation Pharmaceutical Research Center, Korea Institute of Toxicology, Daejeon 34114, Korea.; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Human and Environmental Toxicology Program, University of Science and Technology, Daejeon 34113, Korea.

The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology
|January 26, 2016
PubMed

Insights

Dihydropyridine calcium channel blockers (CCBs) like nicardipine and amlodipine may not increase arrhythmia risk as they also inhibit potassium channels, unlike isradipine. This study clarifies their distinct electrophysiological effects on cardiac action potentials.

Area of Science:

  • Cardiovascular Pharmacology
  • Electrophysiology
  • Ion Channel Modulation

Background:

  • Dihydropyridine calcium channel blockers (CCBs) are crucial for cardiovascular disease treatment.
  • Reduced calcium channel current (I Ca) by CCBs can shorten action potential duration (APD), potentially causing arrhythmia.
  • Understanding the differential effects of CCBs on cardiac ion channels is vital for safety.

Purpose of the Study:

  • To investigate the electrophysiological effects of nicardipine (NIC), isradipine (ISR), and amlodipine (AML) on cardiac action potential duration (APD).
  • To examine the impact of these CCBs on key cardiac ion currents, including I Ca, I Kr, I Ks, and I Na.
  • To determine if inhibition of repolarizing currents by CCBs could offset APD shortening.

Main Methods:

  • Electrophysiological recordings in rabbit Purkinje fibers.
  • Concentration-dependent inhibition assays of I Ca in rat cardiomyocytes.
  • Voltage-gated ion channel current measurements (I Kr, I Ks, I Na).

Main Results:

  • NIC, ISR, and AML demonstrated similar potency in blocking I Ca (IC50 values in nM range).
  • ISR significantly shortened both APD50 and APD90 at 1 µM; NIC and AML only shortened APD50 up to 30 µM.
  • NIC and AML concentration-dependently inhibited I Kr and I Ks, while ISR showed only partial inhibition (<50% at 30 µM).
  • All three CCBs inhibited I Na to a similar extent.

Conclusions:

  • NIC and AML inhibit both I Ca and repolarizing K+ currents (I Kr, I Ks).
  • The inhibition of I Kr and I Ks by NIC and AML may counteract the AP-shortening effects of I Ca blockade.
  • ISR's limited effect on I Kr and I Ks suggests a potentially higher risk of APD shortening and associated arrhythmias compared to NIC and AML.

Keywords:
AntihypertensivesCardiac action potentialsCardiac repolarizationDihydropyridine calcium channel blockersIon channels

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