[cAMP, calmodulin-dependent stimulation and stability to proteolysis of Ca 2+ transport in the heart sarcoplasmic reticulum]
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Hypoxic heart muscle shows increased calmodulin, but its effect on calcium transport in the sarcoplasmic reticulum remains unchanged. Protein kinase activity decreases, impacting calcium transport, but phosphorylation can restore function.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Context:
- Hypoxia in cardiomyocytes leads to increased calmodulin levels.
- Calcium (Ca2+) transport in the sarcoplasmic reticulum (SR) is crucial for cardiac function.
- Ischemia affects endogenous cAMP-dependent protein kinase activity.
Purpose:
- To investigate the role of calmodulin and protein kinase activity in cardiomyocyte calcium transport during myocardial hypoxia and ischemia.
- To understand the impact of altered protein kinase activity on Ca2+ transport in the SR.
Summary:
- Calmodulin levels increase in hypoxic cardiomyocyte cytosol without altering its effect on SR Ca2+ transport.
- Decreased endogenous cAMP-dependent protein kinase activity in ischemia correlates with reduced trypsinolysis resistance of SR Ca2+ transport and Ca-ATPase activation.
- Exogenous protein kinase and cAMP restore the protective effect of phosphorylation on SR Ca2+ transport in trypsin-treated hypoxic cardiomyocytes.
Impact:
- This research elucidates the complex interplay between calmodulin, protein kinase, and calcium handling in the ischemic heart.
- Findings suggest potential therapeutic targets for preserving cardiac function during ischemic events.
- Understanding these molecular mechanisms is vital for developing strategies against heart disease.
Abstract:
The calmodulin content in cardiomyocyte cytosol of hypoxic myocardium is increased compared to normal level. This is unaccompanied by differences in the stimulating effect of calmodulin on Ca2+ transport in sarcoplasmic reticulum (SR) of ischemic heart. The decrease of the endogenous cAMP-dependent protein kinase activity in ischemia is associated with the lowered resistance to trypsinolysis of Ca2+ transport in SR (trypsin/microsomal protein ratio is 1:10) with simultaneous Ca-ATPase activation. In the presence of exogenous protein kinase and cAMP the protective effect of phosphorylation on Ca2+ transport in SR vesicles of hypoxic cardiomyocytes treated with trypsin for 10 min reaches the same level as in intact heart.