Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization

• 영문명: Comparison of electrophysiological effects of calcium channel blockers on cardiac repolarization
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Hyang-Ae Lee Sung-Ae Hyun Sung-Gurl Park Ki-Suk Kim Sung Joon Kim
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제20권 제1호, 119~127쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2016.01.01

영문 초록

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 electrophysiologicaleffects 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 μM whereas NIC and AML shortened APD₅₀ but not APD₉₀ up to 30 μM. 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 μM). 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.

키워드

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