Cardiac nicotinic receptors show β-subunit-dependent compensatory changes
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- cardiac cholinergic system, heart physiology, nicotinic receptor, receptor plasticity,
- MeSH
- Acetylcholine pharmacology MeSH
- Muscarinic Antagonists pharmacology MeSH
- Atropine pharmacology MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Hexamethonium pharmacology MeSH
- Isoproterenol pharmacology MeSH
- Myocardium metabolism MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Neostigmine pharmacology MeSH
- Receptors, Nicotinic metabolism MeSH
- Heart drug effects MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Acetylcholine MeSH
- Muscarinic Antagonists MeSH
- Atropine MeSH
- Cholinesterase Inhibitors MeSH
- Hexamethonium MeSH
- Isoproterenol MeSH
- Neostigmine MeSH
- Receptors, Nicotinic MeSH
Nicotinic receptors (NRs) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2-subunits and β4-subunits may substitute for each other. In our study, we assessed the hypothetical β-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4-subunits and α3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.NEW & NOTEWORTHY In the present study, we observed an increase in mRNA levels of the β2 NR subunit in β4-/- hearts but not vice versa, thus supporting the hypothesis of β NR subunit plasticity that depends on the specific type of missing β-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of β4-/- mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.
Biomedical Research Centre University Hospital Hradec Kralove Hradec Kralove Czech Republic
Department of Pharmacology Slovak Medical University in Bratislava Bratislava Slovakia
References provided by Crossref.org
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