AI Article Synopsis
- Higher heart rate (HR) is linked to negative outcomes in several heart conditions, like hypertension and heart failure, and is regulated by pacemaker cells in the sinoatrial node.
- The HCN4 channel, a key player in this process, generates the I current that influences HR.
- Ivabradine, the only available HCN inhibitor, lowers HR and is approved for certain cardiac conditions in many countries, and this review discusses its function, mechanism, and clinical effects in diseases such as heart failure and coronary artery disease.
Article Abstract
Higher heart rate (HR) is independently related to worse outcomes in various cardiac diseases, including hypertension, coronary artery disease, and heart failure (HF). HR is determined by the pacemaker activity of cells within the sinoatrial node. The hyperpolarization-activated cyclic nucleotide-gated (HCN) 4 channel, one of 4 HCN isoforms, generates the I current and plays an important role in the regulation of pacemaker activity in the sinoatrial node. Ivabradine is a novel and only available HCN inhibitor, which can reduce HR and has been approved for stable angina and chronic HF in many countries other than Japan. In this review, we summarize the current knowledge of the HCN4 channel and ivabradine, including the function of HCN4 in cardiac pacemaking, the mechanism of action of I inhibition by ivabradine, and the pharmacological and clinical effects of ivabradine in cardiac diseases as HF, coronary artery disease, and atrial fibrillation.
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| http://dx.doi.org/10.1253/circj.CJ-18-1184 | DOI Listing |
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