Monasky Michelle M, Micaglio Emanuele, D'Imperio Sara, Pappone Carlo
Arrhythmology Department, IRCCS Policlinico San Donato, San Donato Milanese, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Front Cardiovasc Med. 2021 Dec 23;8:782596. doi: 10.3389/fcvm.2021.782596. eCollection 2021.
Ajmaline is an anti-arrhythmic drug that is used to unmask the type-1 Brugada syndrome (BrS) electrocardiogram pattern to diagnose the syndrome. Thus, the disease is defined at its core as a particular response to this or other drugs. Ajmaline is usually described as a sodium-channel blocker, and most research into the mechanism of BrS has centered around this idea that the sodium channel is somehow impaired in BrS, and thus the genetics research has placed much emphasis on sodium channel gene mutations, especially the gene , to the point that it has even been suggested that only the gene should be screened in BrS patients. However, pathogenic rare variants in are identified in only 20-30% of cases, and recent data indicates that variants are actually, in many cases, prognostic rather than diagnostic, resulting in a more severe phenotype. Furthermore, the misconception by some that ajmaline only influences the sodium current is flawed, in that ajmaline actually acts additionally on potassium and calcium currents, as well as mitochondria and metabolic pathways. Clinical studies have implicated several candidate genes in BrS, encoding not only for sodium, potassium, and calcium channel proteins, but also for signaling-related, scaffolding-related, sarcomeric, and mitochondrial proteins. Thus, these proteins, as well as any proteins that act upon them, could prove absolutely relevant in the mechanism of BrS.
阿义马林是一种抗心律失常药物，用于揭示1型 Brugada 综合征（BrS）的心电图模式以诊断该综合征。因此，该疾病的核心定义为对这种或其他药物的特定反应。阿义马林通常被描述为一种钠通道阻滞剂，并且大多数关于 BrS 机制的研究都围绕着这样一种观点，即 BrS 中的钠通道以某种方式受损，因此遗传学研究非常重视钠通道基因突变，尤其是该基因，甚至有人建议在 BrS 患者中只应筛查该基因。然而，仅在20%-30%的病例中发现该基因的致病性罕见变异，并且最近的数据表明，在许多情况下，该基因变异实际上是预后性的而非诊断性的，会导致更严重的表型。此外，一些人认为阿义马林仅影响钠电流的误解是有缺陷的，因为阿义马林实际上还作用于钾电流、钙电流以及线粒体和代谢途径。临床研究已将几个候选基因与 BrS 相关联，这些基因不仅编码钠、钾和钙通道蛋白，还编码信号相关、支架相关、肌节相关和线粒体蛋白。因此，这些蛋白质以及作用于它们的任何蛋白质在 BrS 的机制中可能绝对相关。
