Altered dose response to β-agonists in SERCA1a-expressing hearts ex vivo and in vivo

H965, 2002; 10.1152/ajpheart.00078.2002. —In this study we evaluated the contractile characteristics of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)1a-expressing hearts ex vivo and in vivo and in particular their response to β-adrenergic stimulation. Analysis of isolated, work-performing hearts revealed that transgenic (TG) hearts develop much higher maximal rates of contraction and relaxation than wild-type (WT) hearts. Addition of isoproterenol only moderately increased the maximal rate of relaxation (+20%) but did not increase contractility or decrease relaxation time in TG hearts. Perfusion with varied buffer Ca2+ concentrations indicated an altered dose response to Ca2+. In vivo TG hearts displayed fairly higher maximal rates of contraction (+ 25%) but unchanged relaxation parameters and a blunted but significant response to dobutamine. Our study also shows that the phospholamban (PLB) level was decreased (−40%) and its phosphorylation status modified in TG hearts. This study clearly demonstrates...