Isaev Dmytro, Shabbir Waheed, Dinc Ege Y, Lorke Dietrich E, Petroianu Georg, Oz Murat
Department of Cellular Membranology, Bogomoletz Institute of Physiology, Kiev, Ukraine.
Department of Medicine, Division of Nephrology and Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, United States.
Front Pharmacol. 2022 Feb 3;13:821758. doi: 10.3389/fphar.2022.821758. eCollection 2022.
Cannabidiol (CBD), a major non-psychotropic cannabinoid found in the Cannabis plant, has been shown to exert anti-nociceptive, anti-psychotic, and anti-convulsant effects and to also influence the cardiovascular system. In this study, the effects of CBD on major ion currents were investigated using the patch-clamp technique in rabbit ventricular myocytes. CBD inhibited voltage-gated Na and Ca channels with IC values of 5.4 and 4.8 µM, respectively. In addition, CBD, at lower concentrations, suppressed ion currents mediated by rapidly and slowly activated delayed rectifier K channels with IC of 2.4 and 2.1 µM, respectively. CBD, up to 10 μM, did not have any significant effect on inward rectifier and transient outward currents. The effects of CBD on these currents developed gradually, reaching steady-state levels within 5-8 min, and recoveries were usually slow and partial. Hill coefficients higher than unity in concentration-inhibition curves suggested multiple CBD binding sites on these channels. These findings indicate that CBD affects cardiac electrophysiology by acting on a diverse range of ion channels and suggest that caution should be exercised when CBD is administered to carriers of cardiac channelopathies or to individuals using drugs known to affect the rhythm or the contractility of the heart.
大麻二酚(CBD)是大麻植物中一种主要的非精神活性大麻素,已被证明具有抗伤害感受、抗精神病和抗惊厥作用,还能影响心血管系统。在本研究中,采用膜片钳技术在兔心室肌细胞中研究了CBD对主要离子电流的影响。CBD抑制电压门控钠通道和钙通道,其半数抑制浓度(IC)分别为5.4和4.8 μM。此外,较低浓度的CBD抑制由快速和缓慢激活的延迟整流钾通道介导的离子电流,其IC分别为2.4和2.1 μM。高达10 μM的CBD对内向整流电流和瞬时外向电流没有任何显著影响。CBD对这些电流的作用逐渐显现,在5 - 8分钟内达到稳态水平,恢复通常缓慢且不完全。浓度抑制曲线中的希尔系数高于1,表明这些通道上存在多个CBD结合位点。这些发现表明,CBD通过作用于多种离子通道来影响心脏电生理,并提示当给患有心脏通道病的患者或使用已知会影响心脏节律或收缩性的药物的个体使用CBD时应谨慎。