Attenuated β-adrenergic response in calcium/calmodulin-dependent protein kinase IV-knockout mice.
Action Potentials
/ drug effects
Adrenergic beta-Agonists
/ pharmacology
Adrenergic beta-Antagonists
/ pharmacology
Animals
Baroreflex
/ drug effects
Calcium Channels
/ genetics
Calcium-Calmodulin-Dependent Protein Kinase Type 4
/ genetics
Heart
/ diagnostic imaging
Heart Rate
/ drug effects
Isoproterenol
/ pharmacology
Mice
Mice, Knockout
Myocytes, Cardiac
/ metabolism
Optical Imaging
Propranolol
/ pharmacology
Signal Transduction
/ drug effects
Transcriptome
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
28
08
2020
accepted:
26
03
2021
entrez:
15
4
2021
pubmed:
16
4
2021
medline:
29
9
2021
Statut:
epublish
Résumé
In the present study, we examined the importance of Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) in the regulation of cardiac function using genetically modified CaMKIV-null mice. RT-PCR analysis revealed decreased expression of voltage-dependent calcium channels in the cardiac myocytes of CaMKIV-null mice compared with wild-type mice. CaMKIV-null mice showed shortened QT time on electrocardiograms. Pharmacological analysis revealed decreased responsiveness to the β-adrenergic blocker propranolol in CaMKIV-null mice, whereas the plasma norepinephrine level was not affected. CaMKIV-null mice showed decreased baroreflex on electrocardiograms. Heart rate variability analysis showed unstable R-R intervals, a decreased low frequency power/high frequency power (LF/HF) ratio, and increased standard deviation of the normal to normal R-R intervals (SDNN) in CaMKIV-null mice, suggesting decreased responsiveness to β-adrenergic stimulation in CaMKIV-null mice. Atrial contraction analysis and cardiac action potential recording showed a decreased response to the β-adrenoceptor agonist isoproterenol in CaMKIV-null mice. Furthermore, fluorescence imaging in a CRE-hrGFP assay revealed a decreased response to isoproterenol in CaMKIV-null cardiac myocytes. Taken together, our data strongly suggest a significant effect of CaMKIV gene ablation on cardiac β-adrenergic signal transduction.
Identifiants
pubmed: 33857227
doi: 10.1371/journal.pone.0249932
pii: PONE-D-20-27116
pmc: PMC8049319
doi:
Substances chimiques
Adrenergic beta-Agonists
0
Adrenergic beta-Antagonists
0
Calcium Channels
0
Propranolol
9Y8NXQ24VQ
Calcium-Calmodulin-Dependent Protein Kinase Type 4
EC 2.7.11.17
Isoproterenol
L628TT009W
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0249932Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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