Gene Expression Of Atrial L-type Calcium Channel And Modulatory Receptors In Patients With Atrial Fibrillation

Objective The purpose of this study is to investigate the gene expression of atrial L-type calcium channel(LCC) subunits and modulatory receptors and to pursue the molecular mechanism of L-type calcium current (ICaL) changes in patients with atrial fibrillation(AF). Methods and Results There are two parts in the present study, in which the mRNA expression of the cardiac LCC subunitsα1C,β1a,β1b/1c and α2/δ1 and modulatory factor such as 5-hydroxytryptamine type 4-,β1-,β2-adrenergic receptors were respectively detected by semi-quantitative RT-PCR in atrial tissue of patients with chronic atrial fibrillation(CAF) or paroxysmal atrial fibrillation (PAF) compared to patients in sinus rhythm(SR) who all had underlying rheumatic heart disease (RHD) or congenital heart disease (CHD). Compared to patients in sinus rhythm, mRNA expression of theα1C subunit was significantly reduced in patients with CAF, and mildly down-regulated in patients with PAF. Significant correlation was found between the mRNA expression of α1c subunit and mean atrial rate and left arial diameter. There was significant difference between above three groups after the effect of atrial diameter was corrected by one-way ANOVA. The mRNA expression of theβ1a and β1c subunit were unchanged in either CAF or PAF patients. The mRNA amount of β1b,β1b/1c was down-regulated in CAF patients. While in patients with PAF, it remained unchanged. In both CAF and PAF patients, the abundance of α2/δ1 subunit transcription was significantly decreased. There were reductions in mRNA expression of 5-HT4-R in both CAF and PAF groups. There were no changes in mRNA of β1-AR and β2-AR in either CAF or PAF patients. Conclution The down-regulated mRNA transcription of L-type calcium channel plays an important role in atrial electrical remodeling in AF. The molecular mechanism of ICaL remodeling may be due to the reduced number of LCC in per atrial tissue of patients with CAF, or the diminished regulatory function by auxiliary L-type calcium channel subunits and modulatory 5-HT4-receptor of LCC. The ICaL remodeling in patients with PAF may be related to the diminished regulatory function by auxiliary α2/δ1 subunit and 5-HT4-receptor of LCC. α2/δ1 subunit and 5-HT4-receptor may be one of the earliest changed genes in patients with AF.