The endogenous cardiac sarcoplasmic reticulum Ca2+/calmodulin‐dependent kinase is activated in response to β‐adrenergic stimulation and becomes Ca2+‐independent in intact beating hearts

Abstract
We investigated the effects of β‐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 β‐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.

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