Soldatov Nikolai M
Humgenex, Inc., Kensington, MD 20895, USA.
Curr Mol Pharmacol. 2015;8(1):32-42. doi: 10.2174/1874467208666150507093258.
The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by increasing the membrane permeability to Ca(2+), a major signal for cardiac muscle contraction, regulation of vascular tone and CREB-dependent transcriptional activation. CACNB2 is one of the four homologous genes coding for the auxiliary Cavβ subunits, which are important modulators of the Ca(2+) channel activity. Five serious mental disorders - autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia, - and three major cardiovascular diseases - hypertension, heart failure and sudden cardiac death, - have recently been linked to the CACNB2 gene coding for the Cavβ2 subunits. Here I will focus on the Cavβ2-specific molecular determinant β2-CED as an emerging pharmacological target.
电压门控性Cav1.2钙通道通过增加细胞膜对Ca(2+)的通透性来响应膜去极化,Ca(2+)是心肌收缩、血管张力调节和CREB依赖的转录激活的主要信号。CACNB2是编码辅助性Cavβ亚基的四个同源基因之一,这些亚基是Ca(2+)通道活性的重要调节因子。最近,五种严重精神障碍——自闭症谱系障碍、注意力缺陷多动障碍、双相情感障碍、重度抑郁症和精神分裂症,以及三种主要心血管疾病——高血压、心力衰竭和心源性猝死,都与编码Cavβ2亚基的CACNB2基因有关。在此,我将重点关注作为新兴药理学靶点的Cavβ2特异性分子决定因素β2-CED。