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

Huke S, Prasad V, Nieman ML, Nattamai KJ, Grupp IL, Lorenz JN, Periasamy M
Am J Physiol Heart Circ Physiol. 2002 283 (3): H958-65

PMID: 12181124 · DOI:10.1152/ajpheart.00078.2002

In this study we evaluated the contractile characteristics of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)1a-expressing hearts ex vivo and in vivo and in particular their response to beta-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 Ca(2+) concentrations indicated an altered dose response to Ca(2+). 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 that increases in SERCA protein level alter the beta-adrenergic response and affect the phosphorylation of PLB. Interestingly, the overall cardiac function in the live animal is only slightly enhanced, suggesting that (neuro)hormonal regulations may play an important role in controlling in vivo heart function.

MeSH Terms (19)

Adrenergic beta-Agonists Animals Calcium Calcium-Binding Proteins Calcium-Transporting ATPases Dobutamine Dose-Response Relationship, Drug Female In Vitro Techniques Isoproterenol Male Mice Mice, Transgenic Myocardial Contraction Myocardium Phosphorylation Receptors, Adrenergic, beta Sarcoplasmic Reticulum Sarcoplasmic Reticulum Calcium-Transporting ATPases

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