Vakhitova Iu V, Farafontova E I, Khisamutdinova R Iu, Iunusov V M, Cypasheva I P, Iunusov M S
Bioorg Khim. 2013 Jan-Feb;39(1):105-16. doi: 10.1134/s1068162013010111.
Allapinine (lappaconitine hydrobromide) is a drug for the treatment of cardiac arrhythmias, it shows IC class antiarrhythmics properties. Its action mechanism is associated with blockade of Na(+)-channels with subsequent inhibition of the depolarization rate and, consequently, of the slowing and reducing the excitability of the cardiac conduction system. At the moment, it is not established, what factors are associated with side effects of Allapinine, and therefore it seems important to study the molecular mechanisms of its action. The target genes were identified in a rat model of aconitine-induced arrhythmia using a commercial kit "Rat Neuroscience Ion Channels & Transporters RT2 Profiler PCR Array" (SABioscienses). Comparison of the expression of 84 genes in the experimental (aconitine arrhythmias/Allapinine) and control (aconitine arrhythmias/saline) animals revealed changes in the mRNA level of 18 genes. It has been shown an increase in mRNA levels of genes encoding various types of K(+)-channels (kcna6, kcnj1, kcnj4, kcnq2, kcnq4), Ca(2+)-channel (cacna 1g), vesicular acetylcholine transporter (slc 18a3). Decrease in the mRNA level was observed for genes encoding the Na(+)-channel (scn8a), K(+)-channels (kcne 1, kcns 1), membrane transporters (atp4a, slc6a9). Taken together, it appears that the effect of Allapinine on aconitine--induced arrhythmias is due to modulation of genes encoding Na(+)-, K(+)-, Ca(2+)-channels, conducting ionic currents (I(Na), I(to), I(Ks), I(K1), I(CaT)), which are involved in the formation of different phases of the action potential. The effect of the drug on the mRNA levels of genes encoding the acetylcholine and glycine transporters, suggesting the participation of these neurotransmitters in the mechanisms of anti-arrhythmic properties of the Allapinine.
阿拉平宁（氢溴酸拉帕替尼）是一种用于治疗心律失常的药物，具有ⅠC类抗心律失常特性。其作用机制与阻断Na⁺通道相关，随后抑制去极化速率，进而减慢并降低心脏传导系统的兴奋性。目前，尚不清楚与阿拉平宁副作用相关的因素，因此研究其作用的分子机制似乎很重要。使用商业试剂盒“大鼠神经科学离子通道与转运体RT2 Profiler PCR阵列”（SABioscienses）在乌头碱诱导的心律失常大鼠模型中鉴定目标基因。比较实验（乌头碱心律失常/阿拉平宁）和对照（乌头碱心律失常/生理盐水）动物中84个基因的表达，发现18个基因的mRNA水平发生了变化。已显示编码各种类型K⁺通道（kcna6、kcnj1、kcnj4、kcnq2、kcnq4）、Ca²⁺通道（cacna 1g）、囊泡乙酰胆碱转运体（slc 18a3）的基因的mRNA水平增加。观察到编码Na⁺通道（scn8a）、K⁺通道（kcne 1、kcns 1）、膜转运体（atp4a、slc6a9）的基因的mRNA水平降低。综上所述，阿拉平宁对乌头碱诱导的心律失常的作用似乎是由于调节了编码Na⁺、K⁺、Ca²⁺通道的基因，这些通道传导离子电流（I(Na)、I(to)、I(Ks)、I(K1)、I(CaT)），参与动作电位不同阶段的形成。该药物对编码乙酰胆碱和甘氨酸转运体的基因的mRNA水平有影响，表明这些神经递质参与了阿拉平宁抗心律失常特性的机制。
