Cardiac nicotinic receptors show β-subunit dependent compensatory changes

Am J Physiol Heart Circ Physiol. 2021 Mar 26. doi: 10.1152/ajpheart.00995.2020. Online ahead of print.ABSTRACTNicotinic receptors (NR) 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 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 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...

Source: American Journal of Physiology. Heart and Circulatory Physiology - March 26, 2021 Category: Physiology Authors: Katarina Targosova Matej Kucera Zuzana Kilianova Lubica Slobodova Kristina Szmicsekova Anna Hrabovska Source Type: research