Molecular and electrical remodeling of ion channels determining action potential duration has been proposed as a major mechanism in chronic atrial fibrillation. We investigated the mRNA expression of the cardiac L-type Ca2+-channel subunits alpha1c, alpha2/delta1, beta1a, and beta1b/c in atrial tissue of patients with chronic atrial fibrillation compared to patients in sinus rhythm. In addition, the mRNA expression of the 5-hydroxytryptamine type 4-, beta1-, and beta2-adrenergic receptors, which are known to stimulate the L-type Ca2+-current in human atrium, was analyzed and the effect of chronic beta-blocker treatment on the mRNA expression of these receptors and of the L-type Ca2+-channel subunits was assessed. Total RNA was isolated from right atrial appendages of patients in sinus rhythm and of patients with chronic atrial fibrillation. Then, semiquantitative RT-PCR using 18S RNA as the "housekeeping gene" was performed. In patients with chronic atrial fibrillation, there were only mild reductions in mRNA expression of the alpha1c-subunit (-15.5 %, p = 0.13), and of the beta1-subunit isoforms a and c (-13.3 %, p = 0.14 and -16.6%, p = 0.18, respectively). However, mRNA expression of the alpha2/delta1-subunit (-31.5 %, p < 0.01) and of the beta1-subunit isoform b (-39.9 %, p < 0.0005) was significantly reduced in patients with chronic AF. Taken together, the mRNA expression of the beta1-subunit isoforms b and c, which are splice variants, was significantly down-regulated by 26.5 % (p < 0.05) in these patients. The analysis of the beta1c/beta1b ratio resulted in a significant shift by 39.2 % (p < 0.0001) in favor of beta1c in patients with chronic atrial fibrillation. In the AF patients, the abundance of the 5-HT4-receptor transcript was significantly reduced by 36 % (p < 0.05). The beta-adrenoreceptor transcription was unchanged. In both SR and AF patients, chronic beta-blocker treatment did neither significantly effect the mRNA expression of the L-type Ca2+-channel subunits, the beta-adrenoreceptor subtypes 1 and 2, nor that of the 5-HT4-receptor. Our data show that chronic AF is associated with a decrease in the atrial mRNA amount of auxiliary subunits of the L-type Ca2+-channel and of the 5-HT4-receptor. This supports the hypothesis that the observed alterations in mRNA transcription in AF patients may lead to a decrease in the availability of functional L-type Ca2+-channels and 5-HT4-receptors and/or reduce L-type Ca2+-current amplitude and density, thus, promoting and stabilizing the arrhythmia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.