| First Author | Myagmar BE | Year | 2017 |
| Journal | Circ Res | Volume | 120 |
| Issue | 7 | Pages | 1103-1115 |
| PubMed ID | 28219977 | Mgi Jnum | J:261969 |
| Mgi Id | MGI:6156745 | Doi | 10.1161/CIRCRESAHA.117.310520 |
| Citation | Myagmar BE, et al. (2017) Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent. Circ Res 120(7):1103-1115 |
| abstractText | RATIONALE: It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), beta1, beta2, beta3, alpha1A, and alpha1B. The beta1 and beta2 are thought to be the dominant myocyte ARs. OBJECTIVE: Quantify the 5 cardiac ARs in individual ventricular myocytes. METHODS AND RESULTS: We studied ventricular myocytes from wild-type mice, mice with alpha1A and alpha1B knockin reporters, and beta1 and beta2 knockout mice. Using individual isolated cells, we measured knockin reporters, mRNAs, signaling (phosphorylation of extracellular signal-regulated kinase and phospholamban), and contraction. We found that the beta1 and alpha1B were present in all myocytes. The alpha1A was present in 60%, with high levels in 20%. The beta2 and beta3 were detected in only approximately 5% of myocytes, mostly in different cells. In intact heart, 30% of total beta-ARs were beta2 and 20% were beta3, both mainly in nonmyocytes. CONCLUSION: The dominant ventricular myocyte ARs present in all cells are the beta1 and alpha1B. The beta2 and beta3 are mostly absent in myocytes but are abundant in nonmyocytes. The alpha1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with beta1 and alpha1B only; 60% that also have the alpha1A; and 5% each that also have the beta2 or beta3. The results raise cautions in experimental design, such as receptor overexpression in myocytes that do not express the AR normally. The data suggest new paradigms in cardiac adrenergic signaling mechanisms. |
