title: Mechanism of adenosine 3',5'-monophosphate (cAMP)-induced increase in Ca2+ uptake by the sarcoplasmic reticulum in functionally skinned myocardial fibers.
abstract: The increased rate of Ca2+ uptake and ATPase activity in isolated cardiac sarcoplasmic reticulum (SR) by adenosine 3',5'-monophosphate (cAMP) has been shown to be activated by a cAMP-dependent protein kinase (cAMP kinase). Functionally skinned myocardial fiber preparations were used to study the mechanisms of cAMP action on the SR at the same time that tension was monitored. cAMP effects were studied on Ca2+ -activated tension of the contractile proteins, and on Ca2+ uptake and release from the SR using caffeine-induced tension transients. Neither cyclic AMP (0.1-5 microM) nor the catalytic subunit of cAMP kinase (0.1-1 microM) (PK-C) significantly changed either the maximal or the submaximal Ca2+ -activated tension. The areas of the tension transients were unchanged when cAMP was present in the releasing solution (release phase), and were significantly increased up to a mean of about 80% when cAMP or PK-C was present in the Ca2+ loading solutions (uptake phase). The increased tension transient was blocked by heat-stable inhibitor of cAMP kinase. We conclude that cAMP-induced increases in Ca2+ uptake by the SR could play an important role in the positive inotropic effect. cAMP kinase could thus play a crucial role in the regulation of myocardial contractility.
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D003285:Contractile Proteins / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003285:Contractile Proteins; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D000242:Cyclic AMP; D002118:Calcium