Phospholamban mediates the β-adrenergic-enhanced Ca2+ uptake in mammalian ventricular myocytes

J. S K Sham, Larry Jones, M. Morad

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Abstract

To probe the molecular mechanism responsible for the relaxant effect of catecholamines in heart muscle, we studied the effect of a monoclonal antibody (2D12) against phospholamban in intact whole cell clamped guinea pig ventricular myocytes, in which intracellular Ca2+ transient and Ca2+ current were simultaneously measured. The antibody stimulated Ca2+ uptake in guinea pig ventricular sarcoplasmic reticular vesicles, shifting the apparent dissociation constant for activation by Ca2+ from 200 to 60 nM. The stimulatory effect of the antibody could be mimicked by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent kinase and could be blocked by phospholamban peptide 2-25. Dialysis of ventricular myocytes with the antibody enhanced the rate of uptake of Ca2+ and siguificantly suppressed the ability of isoproterenol to enhance the rate of uptake and release of Ca2+ by depolarizing pulses. These data suggest that not only is phosphorylation of phospholamban crucial in sequestration of Ca2+ by the sarcoplasmic reticulum, but that this process may account for the catecholamine-enhanced rate of Ca2+ uptake release in heart muscle.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume261
Issue number4 30-4
StatePublished - 1991
Externally publishedYes

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Adrenergic Agents
Muscle Cells
Catecholamines
Antibodies
Myocardium
Guinea Pigs
Molecular Probes
Sarcoplasmic Reticulum
Isoproterenol
Cyclic AMP
Dialysis
Catalytic Domain
Phosphotransferases
Monoclonal Antibodies
Phosphorylation
Peptides
phospholamban

Keywords

  • calcium transient
  • cardiac relaxation
  • monoclonal antibody
  • sarcoplasmic reticulum calcium pump

ASJC Scopus subject areas

  • Physiology

Cite this

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abstract = "To probe the molecular mechanism responsible for the relaxant effect of catecholamines in heart muscle, we studied the effect of a monoclonal antibody (2D12) against phospholamban in intact whole cell clamped guinea pig ventricular myocytes, in which intracellular Ca2+ transient and Ca2+ current were simultaneously measured. The antibody stimulated Ca2+ uptake in guinea pig ventricular sarcoplasmic reticular vesicles, shifting the apparent dissociation constant for activation by Ca2+ from 200 to 60 nM. The stimulatory effect of the antibody could be mimicked by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent kinase and could be blocked by phospholamban peptide 2-25. Dialysis of ventricular myocytes with the antibody enhanced the rate of uptake of Ca2+ and siguificantly suppressed the ability of isoproterenol to enhance the rate of uptake and release of Ca2+ by depolarizing pulses. These data suggest that not only is phosphorylation of phospholamban crucial in sequestration of Ca2+ by the sarcoplasmic reticulum, but that this process may account for the catecholamine-enhanced rate of Ca2+ uptake release in heart muscle.",
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T1 - Phospholamban mediates the β-adrenergic-enhanced Ca2+ uptake in mammalian ventricular myocytes

AU - Sham, J. S K

AU - Jones, Larry

AU - Morad, M.

PY - 1991

Y1 - 1991

N2 - To probe the molecular mechanism responsible for the relaxant effect of catecholamines in heart muscle, we studied the effect of a monoclonal antibody (2D12) against phospholamban in intact whole cell clamped guinea pig ventricular myocytes, in which intracellular Ca2+ transient and Ca2+ current were simultaneously measured. The antibody stimulated Ca2+ uptake in guinea pig ventricular sarcoplasmic reticular vesicles, shifting the apparent dissociation constant for activation by Ca2+ from 200 to 60 nM. The stimulatory effect of the antibody could be mimicked by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent kinase and could be blocked by phospholamban peptide 2-25. Dialysis of ventricular myocytes with the antibody enhanced the rate of uptake of Ca2+ and siguificantly suppressed the ability of isoproterenol to enhance the rate of uptake and release of Ca2+ by depolarizing pulses. These data suggest that not only is phosphorylation of phospholamban crucial in sequestration of Ca2+ by the sarcoplasmic reticulum, but that this process may account for the catecholamine-enhanced rate of Ca2+ uptake release in heart muscle.

AB - To probe the molecular mechanism responsible for the relaxant effect of catecholamines in heart muscle, we studied the effect of a monoclonal antibody (2D12) against phospholamban in intact whole cell clamped guinea pig ventricular myocytes, in which intracellular Ca2+ transient and Ca2+ current were simultaneously measured. The antibody stimulated Ca2+ uptake in guinea pig ventricular sarcoplasmic reticular vesicles, shifting the apparent dissociation constant for activation by Ca2+ from 200 to 60 nM. The stimulatory effect of the antibody could be mimicked by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent kinase and could be blocked by phospholamban peptide 2-25. Dialysis of ventricular myocytes with the antibody enhanced the rate of uptake of Ca2+ and siguificantly suppressed the ability of isoproterenol to enhance the rate of uptake and release of Ca2+ by depolarizing pulses. These data suggest that not only is phosphorylation of phospholamban crucial in sequestration of Ca2+ by the sarcoplasmic reticulum, but that this process may account for the catecholamine-enhanced rate of Ca2+ uptake release in heart muscle.

KW - calcium transient

KW - cardiac relaxation

KW - monoclonal antibody

KW - sarcoplasmic reticulum calcium pump

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