Human heart failure: cAMP stimulation of SR Ca2+-ATPase activity and phosphorylation level of phospholamban

Ulrich Schmidt, Roger J. Hajjar, Catherine S. Kim, Djamel Lebeche, Angelia A. Doye, Judith K. Gwathmey
1999 American Journal of Physiology. Heart and Circulatory Physiology  
mey. Human heart failure: cAMP stimulation of SR Ca 2ϩ -ATPase activity and phosphorylation level of phospholamban. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H474-H480, 1999.-Failing human myocardium has been associated with decreased sarcoplasmic reticulum (SR) Ca 2ϩ -ATPase activity. There remains controversy as to whether the regulation of SR Ca 2ϩ -ATPase activity is altered in heart failure or whether decreased SR Ca 2ϩ -ATPase activity is due to changes in SR Ca 2ϩ -ATPase or
more » ... -ATPase or phospholamban expression. We therefore investigated whether alterations in cAMP-dependent phosphorylation of phospholamban may be responsible for the reduced SR Ca 2ϩ -ATPase activity in human heart failure. Protein levels of phospholamban and SR Ca 2ϩ -ATPase, detected by Western blot, were unchanged in failing compared with nonfailing human myocardium. There was decreased responsiveness to the direct activation of the SR Ca 2ϩ -ATPase activity by either cAMP (0.01-100 µmol/l) or protein kinase A (1-30 µg) in failing myocardium. Using the backphosphorylation technique, we observed a decrease of the cAMPdependent phosphorylation level of phospholamban by 20 Ϯ 2%. It is concluded that the impaired SR function in human end-stage heart failure may be due, in part, to a reduced cAMP-dependent phosphorylation of phospholamban. human myocardium; calcium ion; sarcoplasmic reticulum; calcium ion-adenosinetriphosphatase; phospholamban ; adenosine 3Ј,5Ј-cyclic monophosphate 0363-6135/99 $5.00
doi:10.1152/ajpheart.1999.277.2.h474 pmid:10444471 fatcat:e5bdswngpjgglieug3y2smizk4