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

Rationale: It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), beta 1, beta 2, beta 3, alpha 1A, and alpha 1B. The beta 1 and beta 2 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 alpha 1A and alpha 1B knockin reporters, and beta 1 and beta 2 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 beta 1 and alpha 1B were present in all myocytes. The alpha 1A was present in 60%, with high levels in 20%. The beta 2 and beta 3 were detected in only approximate to 5% of myocytes, mostly in different cells. In intact heart, 30% of total beta-ARs were beta 2 and 20% were beta 3, both mainly in nonmyocytes. Conclusion: The dominant ventricular myocyte ARs present in all cells are the beta 1 and alpha 1B. The beta 2 and beta 3 are mostly absent in myocytes but are abundant in nonmyocytes. The alpha 1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with beta 1 and alpha 1B only; 60% that also have the alpha 1A; and 5% each that also have the beta 2 or beta 3. 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.