Regulation of Ca2+-pumping ATPase of heart sarcolemma by a phosphorylation-dephosphorylation Process.
Population
Dog heart sarcolemma vesicles
Comparison
Phosphorylation and dephosphorylation treatments vs Untreated or differently treated vesicles
Design
Preclinical
Authors
Discussion
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Implication
Suggests phosphorylation modulates canine cardiac Ca2+ ATPase; hypothesis-generating for human calcium handling with no clinical implications yet.
Key Points
- To determine how phosphorylation and dephosphorylation processes regulate the activity and kinetic properties of the Ca2+-pumping ATPase in cardiac sarcolemma.
- Isolated canine cardiac sarcolemmal vesicles were assessed for baseline phosphorylation and incorporation of [32P]phosphate from [gamma-32P]ATP.
- Vesicles were treated with phosphorylase phosphatase, phosphorylase b kinase, cAMP-dependent protein kinase inhibitor, or EGTA to evaluate changes in phosphorylation status, Ca2+-ATPase activity, and ATP-dependent Ca2+ uptake.
- Phosphorylase phosphatase pretreatment increased 32P incorporation up to 20-fold while markedly inhibiting Ca2+-ATPase activity and Ca2+ uptake, an effect reversed by ATP preincubation.
- Ca2+-pumping activity was stimulated markedly by phosphorylase b kinase and inhibited by cAMP-dependent protein kinase inhibitor, with both kinase inhibitor and EGTA non-additively preventing rephosphorylation.
- Ca2+ dependence curves of Ca2+ uptake in phospho- and dephosphorylated vesicles indicated that phosphorylation alters the enzyme turnover rate rather than its affinity for Ca2+.
Structured PICO
P
Population
Dog heart sarcolemma vesicles
I
Intervention
Phosphorylation and dephosphorylation treatments (phosphorylase phosphatase, phosphorylase b kinase, cAMP-dependent protein kinase inhibitor)
C
Comparator
Untreated or differently treated vesicles
O
Outcome
Ca2+-ATPase activity and ATP-dependent Ca2+ uptakesurrogate
Phosphorylation regulates the turnover rate of the Ca2+-pumping ATPase in dog heart sarcolemma, suggesting a mechanism for modulating cardiac calcium handling.
Cite This Study
Caroni et al. (1981) studied this question.