Open Collections

UBC Theses and Dissertations

UBC Theses Logo
Featured Collection

UBC Theses and Dissertations

Protein kinase regulation of sarcoplasmic reticulum function in isolated adult rat ventricular myocytes Wientzek, Monika

Abstract

The sarcoplasmic reticulum (SR) is one of the major regulators of the cytosolic Ca2+ concentration in cardiac ventricular muscle cells. In the myocardium, relaxation results from a decrease in cytoplasmic free Ca2+ levels mediated through an efflux of Ca2+ from the cell via the sarcolemmal Na+/Ca2+- exchanger and by the sequestration of 0a2+ by the network SR membranes through the actions of a calcium pump (a Mg2+dependent, Ca2+/K+activated adenosine triphosphatase; Ca2+/K+-ATPase). During an action potential, the Ca2+ stored in the SR is released to the cytoplasm via a Ca2+release channel present in the junctional SR and Ca2+ also enters the cell through voltage-controlled Ca2+ channels in the sarcolemmal membrane. These two processes result in an increase in cytoplasmic Ca2+ concentration which leads to contraction of the myocardium. SR membrane function is regulated in part by the phosphorylation of proteins present in this membrane. Subsequent to 3-adrenergic stimulation of the heart by catecholamines, levels of cAMP are increased leading to the activation of cAMP-dependent protein kinase (PK A). In isolated cardiac SR membrane vesicles and perfused hearts, phosphorylation of an indigenous SR protein, phospholamban, is mediated by PK A. Phosphorylated phospholamban acts as a modulator of the Ca2+/K+-ATPase to stimulate active Ca2+ uptake by increasing the affinity of this enzyme for Ca2+. This stimulation of Ca2+-uptake is the main mechanism by which catecholamines accelerate relaxation in the heart. When phospholamban is in the dephosphorylated state, a cytoplasmic portion of the molecule interacts near the phosphorylation site of the Ca2+-pump to inhibit Ca2+-transport. [More abstract follows]

Item Metadata

Title
Protein kinase regulation of sarcoplasmic reticulum function in isolated adult rat ventricular myocytes
Creator
Wientzek, Monika
Publisher
University of British Columbia
Date Issued
1992
Description
The sarcoplasmic reticulum (SR) is one of the major regulators of the cytosolic Ca2+ concentration in cardiac ventricular muscle cells. In the myocardium, relaxation results from a decrease in cytoplasmic free Ca2+ levels mediated through an efflux of Ca2+ from the cell via the sarcolemmal Na+/Ca2+- exchanger and by the sequestration of 0a2+ by the network SR membranes through the actions of a calcium pump (a Mg2+dependent, Ca2+/K+activated adenosine triphosphatase; Ca2+/K+-ATPase). During an action potential, the Ca2+ stored in the SR is released to the cytoplasm via a Ca2+release channel present in the junctional SR and Ca2+ also enters the cell through voltage-controlled Ca2+ channels in the sarcolemmal membrane. These two processes result in an increase in cytoplasmic Ca2+ concentration which leads to contraction of the myocardium. SR membrane function is regulated in part by the phosphorylation of proteins present in this membrane. Subsequent to 3-adrenergic stimulation of the heart by catecholamines, levels of cAMP are increased leading to the activation of cAMP-dependent protein kinase (PK A). In isolated cardiac SR membrane vesicles and perfused hearts, phosphorylation of an indigenous SR protein, phospholamban, is mediated by PK A. Phosphorylated phospholamban acts as a modulator of the Ca2+/K+-ATPase to stimulate active Ca2+ uptake by increasing the affinity of this enzyme for Ca2+. This stimulation of Ca2+-uptake is the main mechanism by which catecholamines accelerate relaxation in the heart. When phospholamban is in the dephosphorylated state, a cytoplasmic portion of the molecule interacts near the phosphorylation site of the Ca2+-pump to inhibit Ca2+-transport. [More abstract follows]
Extent
3862004 bytes
Genre
Thesis/Dissertation
Type
Text
File Format
application/pdf
Language
eng
Date Available
2009-01-05
Provider
Vancouver : University of British Columbia Library
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
DOI
10.14288/1.0086705
URI
http://hdl.handle.net/2429/3350
Degree
Doctor of Philosophy - PhD
Program
Pharmaceutical Sciences
Affiliation
Pharmaceutical Sciences, Faculty of
Degree Grantor
University of British Columbia
Graduation Date
1992-05
Campus
UBCV
Scholarly Level
Graduate
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.