Anti-CACNB2 monoclonal antibody, clone T9c-2 [Biotin]

Objective: To investigate the changes in expression profile of circulating microRNAs (miRNAs) and the regulatory effect of atrial fibrilation (AF)-related miRNAs on ion channels. Methods: 112 patients with AF were assigned into observation group, and another 112 non-AF people were assigned into control group. Total plasma RNAs were extracted from patients' blood samples. Differentially expressed miRNA-1s were transfected into primary-cultured neonatal rat cardiac myocytes. Results: Compared with control group, significant differences were observed in 15 kinds of miRNAs in observation group. Down-regulation of the expression of miRNAs included hsa-miR-328, hsa-miR-145, hsa-miR-222, hsa-miR-1, hsa-miR-162, hsa-miR-432, and hsa-miR-493b; Up-regulation of the expression included hsa-miR634, hsa-miR-664, hsa-miR-9, hsa-miR-152, hsa-miR-19, hsa-miR-454, hsa-miR-146, and hsa-miR-374a. The expression level of CACNB2 protein in miRNA-1 group was significantly lower than that in blank control group, negative control group, MTmiRNA-1 group, AMO-1 group and miRNA-1+AMO-1 cotransfection group (P < 0.05), while in AMO-1 group, the expression level of CACNB2 protein was significantly higher than that in other groups (P < 0.05). These results indicated that transfected miRNA-1 could significantly inhibit the expression of CACNB2 protein. Conclusions: Circulating miRNAs can be used in studies concerning on the regulation mechanism of the occurrence and development of AF. MiRNA-1 can decrease the intracellular Ca2+ concentration and prevent the AF.

Background - Cardiac ion channelopathies are responsible for an ever- increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST- segment elevation in the right precordial ECG leads, a shorter- than- normal QT interval, and a history of sudden cardiac death. Methods and Results - Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b ( Ca-v beta 2b), CACNA2D1 ( Cav(alpha 2 delta 1)), and CACNA1C tagged with enhanced yellow fluorescent protein ( Ca(v)1.2). Whole- cell patch- clamp studies were performed after 48 to 72 hours. Three probands displaying ST- segment elevation and corrected QT intervals <= 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss- of- function missense mutations in CACNA1C ( A39V and G490R) and CACNB2 ( S481L) encoding the alpha(1)- and beta(2b)- subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Cav1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca-v beta 2b-subunits. Conclusions - This is the first report of loss- of- function mutations in genes encoding the cardiac L- type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter- than- normal QT intervals.