title: 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.
abstract: BACKGROUND
  It is unknown whether every ventricular myocyte expresses all 5 of the cardiac adrenergic receptors (ARs), β1, β2, β3, α1A, and α1B. The β1 and β2 are thought to be the dominant myocyte ARs.
  
  
  OBJECTIVE
  Quantify the 5 cardiac ARs in individual ventricular myocytes.
  
  
  RESULTS
  We studied ventricular myocytes from wild-type mice, mice with α1A and α1B knockin reporters, and β1 and β2 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 β1 and α1B were present in all myocytes. The α1A was present in 60%, with high levels in 20%. The β2 and β3 were detected in only ≈5% of myocytes, mostly in different cells. In intact heart, 30% of total β-ARs were β2 and 20% were β3, both mainly in nonmyocytes.
  
  
  CONCLUSIONS
  The dominant ventricular myocyte ARs present in all cells are the β1 and α1B. The β2 and β3 are mostly absent in myocytes but are abundant in nonmyocytes. The α1A is in just over half of cells, but only 20% have high levels. Four distinct myocyte AR phenotypes are defined: 30% of cells with β1 and α1B only; 60% that also have the α1A; and 5% each that also have the β2 or β3. 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.
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Bat-Erdene
authors.initials: BE
authors.lastname: Myagmar
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: James M
authors.initials: JM
authors.lastname: Flynn
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Cowley
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Philip M
authors.initials: PM
authors.lastname: Swigart
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Megan D
authors.initials: MD
authors.lastname: Montgomery
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Kevin
authors.initials: K
authors.lastname: Thai
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Divya
authors.initials: D
authors.lastname: Nair
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Rumita
authors.initials: R
authors.lastname: Gupta
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: David X
authors.initials: DX
authors.lastname: Deng
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hosoda
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Baker
authors.affiliation: From the Department of Medicine, VA Medical Center, San Francisco, CA (B.-E.M., P.M.C., P.M.S., M.D.M., K.T., D.N., R.G., D.X.D., C.H., A.J.B., P.C.S.); Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco (B.-E.M., P.M.C., M.D.M., D.X.D., C.H., A.J.B., P.C.S.); and Buck Institute for Research on Aging, Novato, CA (J.M.F., S.M.). paul.simpson@ucsf.edu.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D059010:Single-Cell Analysis
chemical_list: D012333:RNA, Messenger; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta
keywords: adrenergic agents; mice, knockout; myocytes, cardiac; receptors, adrenergic; receptors, adrenergic, alpha-1; receptors, adrenergic, beta