The endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin-dependent kinase is activated in response to beta-adrenergic stimulation and becomes Ca2+-independent in intact beating hearts.
We investigated the effects of beta-adrenergic stimulation on the activity of the endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin-dependent protein kinase (SRCaM kinase) in Langendorff-perfused rat hearts. We found that isoproterenol induced generation of autonomous (Ca2+-independent) SRCaM kinase activity to 28 +/- 4.4% of the total activity. Moreover, dephosphorylation of the autonomous SRCaM kinase with protein phosphatase 2A resulted in an enzyme that was again dependent on Ca2+ and calmodulin for its activity. Activation of SRCaM kinase was coupled to phospholamban phosphorylation and activation of the cAMP-signaling system. Our results suggest that the cardiac SRCaM kinase is activated in response to beta-adrenoceptor stimulation. This activation stimulates autophosphorylation at its regulatory domain and converts it to an active Ca2+-independent species that may be the basis for potentiation of Ca2+ transients in the heart.
Baltas
L G
LG
Max Delbrück Centre for Molecular Medicine (MDC), Berlin, Germany. lbaltas@orion.rz.mdc-berlin.de
Karczewski
P
P
Bartel
S
S
Krause
E G
EG
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D000318:Adrenergic beta-Agonists; D002118:Calcium; D002135:Calcium-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D007545:Isoproterenol; D000099211:Phospholamban