Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Institutskaya 3, 142290 Pushchino, Russia.
Department of Cardiovascular Medicine, Center for Regenerative Medicine, Mayo Clinic, Stabile 5, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905, USA.
Int J Mol Sci. 2021 Apr 16;22(8):4135. doi: 10.3390/ijms22084135.
Sarcolemmal α2 adrenoceptors (α2-AR), represented by α2A, α2B and α2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca handling and contractility of cardiomyocytes. Cardiomyocyte-specific targeting of α2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the α2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of α2A, α2B and α2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca current (). Patch-clamp electro-pharmacological studies revealed that the α2-agonist-induced suppression of involves mainly the α2C, to a lesser extent the α2B, and not the α2A isoforms. RT-qPCR evaluation revealed the presence of and (α2B and α2C isoform genes, respectively), but was unable to identify the expression of (α2A isoform gene) in the mouse left ventricle. Immunoblotting confirmed the presence only of the α2B and the α2C proteins in this tissue. The identified α2-AR isoform-linked regulation of in the mouse ventricle provides an important molecular substrate for the cardioprotective targeting.
肌膜 α2 肾上腺素能受体（α2-AR），由 α2A、α2B 和 α2C 三种亚型组成，通过调节心肌细胞的 Ca 处理和收缩能力，在交感神经兴奋时保护心肌。心肌细胞特异性靶向 α2-AR 可以提供心肌局限性应激控制，并增强心脏功能障碍治疗的效果。然而，对于调节心肌细胞功能的 α2-AR 亚型的具体作用，我们知之甚少。本文分析了小鼠心室中 α2A、α2B 和 α2C 亚型的表达谱，并进行了电生理学拮抗剂测定，以评估这些亚型对 L 型 Ca 电流（）抑制的贡献。膜片钳电药理学研究表明，α2-激动剂诱导的抑制主要涉及 α2C，其次是 α2B，而不是 α2A 亚型。RT-qPCR 评估显示存在 和 （分别为 α2B 和 α2C 亚型基因），但无法在小鼠左心室中鉴定出 （α2A 亚型基因）的表达。免疫印迹证实该组织中仅存在 α2B 和 α2C 蛋白。在小鼠心室中鉴定出的 α2-AR 亚型相关的 调节作用为心脏保护性靶向治疗提供了重要的分子基础。
