| First Author | Murakami M | Year | 2021 |
| Journal | PLoS One | Volume | 16 |
| Issue | 4 | Pages | e0249932 |
| PubMed ID | 33857227 | Mgi Jnum | J:304792 |
| Mgi Id | MGI:6695049 | Doi | 10.1371/journal.pone.0249932 |
| Citation | Murakami M, et al. (2021) Attenuated beta-adrenergic response in calcium/calmodulin-dependent protein kinase IV-knockout mice. PLoS One 16(4):e0249932 |
| abstractText | 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 beta-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 beta-adrenergic stimulation in CaMKIV-null mice. Atrial contraction analysis and cardiac action potential recording showed a decreased response to the beta-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 beta-adrenergic signal transduction. |
