Cardiac nicotinic receptors show beta-subunit-dependent compensatory changes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F21%3A10432082" target="_blank" >RIV/00179906:_____/21:10432082 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=y2o7DzIULg" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=y2o7DzIULg</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1152/ajpheart.00995.2020" target="_blank" >10.1152/ajpheart.00995.2020</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cardiac nicotinic receptors show beta-subunit-dependent compensatory changes

Popis výsledku v původním jazyce

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 beta NR subunits suggests that beta 2-subunits and beta 4-subunits may substitute for each other. In our study, we assessed the hypothetical beta-subunit interchangeabil- ity in the heart at the level of mRNA. Using two mutant mice strains lacking beta 2 or beta 4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorffs method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of beta 2 NR subunit was accompanied with decreased relative expression of beta 4-subunits and alpha 3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking beta 2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking beta 4 NR subunit, increased levels of beta 2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in beta 4(-/-) 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 &amp; NOTEWORTHY In the present study, we observed an increase in mRNA levels of the beta 2 NR subunit in beta 4(-/-) hearts but not vice versa, thus supporting the hypothesis of beta NR subunit plasticity that depends on the specific type of missing beta-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of beta 4(-/-) mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.

Název v anglickém jazyce

Cardiac nicotinic receptors show beta-subunit-dependent compensatory changes

Popis výsledku anglicky

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 beta NR subunits suggests that beta 2-subunits and beta 4-subunits may substitute for each other. In our study, we assessed the hypothetical beta-subunit interchangeabil- ity in the heart at the level of mRNA. Using two mutant mice strains lacking beta 2 or beta 4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorffs method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of beta 2 NR subunit was accompanied with decreased relative expression of beta 4-subunits and alpha 3-subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking beta 2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking beta 4 NR subunit, increased levels of beta 2-subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in beta 4(-/-) 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 &amp; NOTEWORTHY In the present study, we observed an increase in mRNA levels of the beta 2 NR subunit in beta 4(-/-) hearts but not vice versa, thus supporting the hypothesis of beta NR subunit plasticity that depends on the specific type of missing beta-subunit. This was accompanied with specific cholinergic adaptations. Nevertheless, isolated hearts of beta 4(-/-) mice showed increased basal heart rate and a higher sensitivity to a high dose of acetylcholine upon adrenergic stimulation.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30105 - Physiology (including cytology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

American Journal of Physiology - Heart and Circulatory Physiology

ISSN

0363-6135

e-ISSN

—

Svazek periodika

320

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

"H1975"-"H1984"

Kód UT WoS článku

000661571000006

EID výsledku v databázi Scopus

2-s2.0-85105254009