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A recent hypothesis about the plasticity of \u03b2 NR subunits suggests that \u03b22-subunits and \u03b24-subunits may substitute for each other. In our study, we assessed the hypothetical \u03b2-subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking \u03b22 or \u03b24 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\u2018s method at basal conditions and after cholinergic and\/or adrenergic stimulation. Lack of \u03b22 NR subunit was accompanied with decreased relative expression of \u03b24-subunits and \u03b13-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking \u03b22 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking \u03b24 NR subunit, increased levels of \u03b22-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in \u03b24<jats:sup>\u2212\/\u2212<\/jats:sup> 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. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY In the present study, we observed an increase in mRNA levels of the \u03b22 NR subunit in \u03b24<jats:sup>\u2212\/\u2212<\/jats:sup> hearts but not vice versa, thus supporting the hypothesis of \u03b2 NR subunit plasticity that depends on the specific type of missing \u03b2-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of \u03b24<jats:sup>\u2212\/\u2212<\/jats:sup> mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation. <\/jats:p>","DOI":"10.1152\/ajpheart.00995.2020","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T16:22:57Z","timestamp":1616775777000},"page":"H1975-H1984","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cardiac nicotinic receptors show \u03b2-subunit-dependent compensatory changes"],"prefix":"10.1152","volume":"320","author":[{"given":"Katarina","family":"Targosova","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matej","family":"Kucera","sequence":"additional","affiliation":[{"name":"Department 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