The role of β3-adrenergic receptor polymorphism on regulation of L-type calcium current and force of contraction in human atrium

• Main Authors: Marandykina, Alina, Zablockaitė, Danguolė, Buzaitė, Odeta, Treinys, Rimantas, Bogdelis, Andrius, Jurevičius, Jonas, Skeberdis, Vytenis Arvydas
• Format: Conference Object
• Language: English
• Published: 2009
• Subjects: Receptors; adrenergic; beta-3; Calcium channels; L-Type; Myocardial contraction; Heart atria; Tezės Clarivate Analytics Web of Science / Theses in Clarivate Analytics Web of Science (T1a); Biologija / Biology (N010); Iceland
• Online Access: http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=223370&Ausgabe=249596&ProduktNr=223832&filename=223370.pdf

Abstracts and program XXII Nordic-Baltic congress of cardiology : Reykjavik, Iceland, June 3-5, 2009 / Guest editors : David O. Arnar, Karl Andersen '3-adrenergic receptor (β3-AR) agonists stimulate L-type Ca2+ current (ICa,L) and force of contraction in human atrium. One nonsynonymous single nucleotide polymorphism Trp64Arg of β3-AR has been reported, which causes weaker cAMP accumulation comparing to Trp64Trp one. Therefore, we examined a role of β3-AR polymorphism in β3-AR agonist CGP12177 and BRL37344 induced stimulation of ICa,L and contraction force in isolated atrial myocytes and atrial trabeculae, respectively, obtained from patients undergoing heart surgery in Kaunas University Hospital (KUH). We used the restriction fragment length polymorphism method to analyze DNA samples for β3-AR polymorphism. Whole-cell patch-clamp technique was used to record ICa,L. Isometric contraction of atrial trabeculae was recorded using a mechanoelectrical force transducer. We examined genotype of 41 control DNA and 61 DNA samples obtained from KUH patients. The rate of Trp64Trp and Trp64Arg genotype was 5% and 7%, respectively. In case of Trp64Trp, CGP12177 (1 μM) and BRL37344 (1 μM) stimulated ICa,L by 64±19% (n=10) and 122±27% (n=22) over control, respectively, and contraction force by 13±3.9% (n=9) and 26±2.7% (n=4) over control, respectively. In case of Trp64Arg, CGP12177 (1 μM) and BRL37344 (1 μM) stimulated ICa,L by 33±4.9% (n=7) and 94±11% (n=3) over control, respectively, and contraction force by 4.2±2.2% (n=2) and 5.3±1.8% (n=2) over control, respectively. Our preliminary results indicate that the efficacy of β3-ARdependent stimulation of ICa,L and contraction force may depend on Trp64Arg polymorphism, however to make a final conclusion a number of Trp64Arg cases must be significantly increased Biologijos katedra Kauno medicinos universiteto Kardiologijos institutas Vytauto Didžiojo universitetas