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Updated: Aug 29, 2026

Impact of Intracardiac Neurons on Cardiac Electrophysiology and Arrhythmogenesis in an Ex Vivo Langendorff System
Published on: May 22, 2018
Altered signal transduction in cardiac ventricle overexpressing A(1)-adenosine receptors
Joachim Neumann1, Peter Boknik, Frank Begrow
1Institut für Pharmakologie und Toxikologie, Universitätsklinikum Münster, Westfälische Wilhelms-Universität, Domagkstrasse 12, D-48129 Münster, Germany.
Objective:
The aim of the present study was to assess the effects of A(1)-adenosine receptor (A1-AR) stimulation in ventricle of A(1)-adenosine receptor overexpressing mice (transgenic mice, TG).
Methods:
Effects of the A(1)-adenosine receptor agonist R-PIA ((-)-N(6)-phenylisopropyladenosine) on phosphorylation of phospholamban (PLB), Ca(2+) transients, Ca(2+) currents and cell shortening were studied in isolated ventricular cardiomyocytes.
Results:
R-PIA alone did not affect contractility in isolated electrically stimulated cardiomyocytes from wild-type mice (WT) or TG. However, after pre-stimulation of beta-adrenoceptors by isoproterenol, R-PIA reduced contractility in cardiomyocytes from WT but increased contractility in TG. Under the same conditions, R-PIA reduced isoproterenol-stimulated currents through L-type Ca(2+) channels, Ca(2+) transients and phosphorylation of PLB in cardiomyocytes from WT. In contrast, R-PIA diminished phospholamban phosphorylation induced by isoproterenol but augmented isoproterenol-elevated currents through L-type Ca(2+) channels, and isoproterenol-heightened Ca(2+) transients in cardiomyocytes from TG.
Conclusions:
We suggest that A(1)-adenosine receptor overexpression reverses the interaction of beta-adrenergic and A(1)-adenosine receptor stimulation, at least in part. Hence, the receptor/effector coupling is dependent on receptor density in this model.
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