Gergs, Ulrich and Buchwalow, Igor B. and Hofmann, Britt and Myslivecek, Jaromir and Janisova, Katerina and Hadova, Katarina and Schettler, Franziska and Keller, Max and Klimas, Jan and Neumann, Joachim (2026) Initial characterization of M2-muscarinic receptor overexpressing mouse heart. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 399. pp. 1467-1479. ISSN 0028-1298, 1432-1912
Full text not available from this repository.Abstract
There are five muscarinic receptor subtypes expressed in the human heart. The main subtype is the M-2-muscarinic receptor. We hypothesized that overexpression of the M-2-muscarinic receptor should augment any contractile effects that are M-2-muscarinic receptor-mediated. Therefore, we generated a transgenic mouse with overexpression of the human M-2-muscarinic receptor under the control of the heart-specific alpha-myosin heavy chain promoter (M-2-TG). We performed contraction experiments with electrically stimulated (1 Hz) left atrial preparations (LA) and spontaneously beating right atrial preparations (RA) from adult M-2-TG or from adult wild-type littermate mice (WT). We confirmed the expression of the human M-2-muscarinic receptor in the mouse heart by reverse transcription polymerase chain reaction (RT-PCR) and radioligand binding experiments at cardiac membranes and tissue sections. We did not detect differences in hematoxylin/eosin staining or Masson/Goldner staining between M-2-TG and WT. We noticed that carbachol (10 nM-10 mu M cumulatively applied) alone or in the presence of 1 mu M isoprenaline reduced the force of contraction (FOC) to a similar extent in LA from M-2-TG and WT. The beating rate in RA was similarly decreased by carbachol alone or by carbachol in the presence of 1 mu M isoprenaline in M-2-TG and WT. Overall, the number of RA that displayed absolute arrhythmias was higher in atria from M-2-TG compared to atria from WT. No arrhythmias were noted in LA from M-2-TG or WT. Stimulation of human M-2-muscarinic receptors induced absolute atrial arrhythmias more often in RA from M-2-TG than in RA from WT. Overexpressed M-2-muscarinic receptors were silent to the force and beating rate.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MUSCARINIC RECEPTORS; ATRIAL-FIBRILLATION; ACETYLCHOLINE; ADENOSINE; STIMULATION; ARRHYTHMIAS; TACHYCARDIA; CARBACHOL; DECREASE; SUBTYPE; Human M-2-muscarinic receptors; Arrhythmia |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2026 08:20 |
| Last Modified: | 28 Jul 2026 08:20 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67623 |
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