Persistent Link:
http://hdl.handle.net/10150/184221
Title:
TAURINE AND THE CARDIAC SARCOLEMMA.
Author:
SEBRING, LESLIE ANN.
Issue Date:
1987
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Taurine is by far the most abundant of the sulfur amino acids, levels in the heart exceeding the combined quantities of all others. Taurine exhibits extensive cardiovascular pharmacology, including inotropic and antiarrhythmic properties. Many of the actions of taurine appear to involve a modulation of calcium availability. The sarcolemma regulates the entry of calcium into the heart. Binding sites on the cardiac sarcolemma provide calcium for contraction and maintain membrane integrity. The effect of taurine on calcium binding to rat heart sarcolemma varies with the buffer. In Tris and the presence of sodium, taurine increases the affinity of the low affinity binding, but decreases the maximal binding of calcium. In the absence of sodium, taurine decreases affinity of the low affinity binding without altering the maximal binding. These effects on low affinity binding, however, are absent in physiological buffers representative of extracellular conditions. In buffers representative of intracellular ionic conditions, taurine increases the high affinity binding of calcium to sarcolemma in a dose-dependent manner. These results suggest that taurine exerts its cardiotonic actions through a modulation of the high affinity calcium binding on the internal aspect of the sarcolemma. Membrane phospholipids are important calcium-binding molecules in cardiac sarcolemma. Heterogeneous vesicles containing phospholipids in a ratio approximating that of rat heart sarcolemma bind significant quantities of calcium. Taurine increases calcium binding to the artificial liposomes in a manner similar to that observed for sarcolemma. Taurine also increases calcium binding to homogeneous vesicles of phosphatidylserine, but not phosphatidylinositol, phosphatidylcholine or phosphatidylethanolamine. Taurine modulation of calcium may not involve a classical protein-ligand interaction, but, instead, a low affinity attraction to sarcolemmal phospholipids. Taurine binds to sarcolemma with low affinity and positive cooperativity at concentrations normally present in the rat heart. Neither β-alanine nor guanidinoethane sulfonate, inhibitors of taurine transport, affect taurine binding. However, hypotaurine and various cations reduce binding. Heterogeneous phospholipid vesicles also bind taurine with positive cooperativity which was enhanced by the inclusion of cholesterol. Taurine associates with homogeneous vesicles of phosphatidylcholine, phosphatidylserine, or phosphatidylethanolamine. Phosphatidylinositol bind little taurine. These studies support the hypothesis that taurine exerts its modulation of sarcolemmal function through an interaction with membrane phospholipids.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Taurine.; Sarcolemma.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Pharmacology and Toxicology; Graduate College
Degree Grantor:
University of Arizona

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleTAURINE AND THE CARDIAC SARCOLEMMA.en_US
dc.creatorSEBRING, LESLIE ANN.en_US
dc.contributor.authorSEBRING, LESLIE ANN.en_US
dc.date.issued1987en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractTaurine is by far the most abundant of the sulfur amino acids, levels in the heart exceeding the combined quantities of all others. Taurine exhibits extensive cardiovascular pharmacology, including inotropic and antiarrhythmic properties. Many of the actions of taurine appear to involve a modulation of calcium availability. The sarcolemma regulates the entry of calcium into the heart. Binding sites on the cardiac sarcolemma provide calcium for contraction and maintain membrane integrity. The effect of taurine on calcium binding to rat heart sarcolemma varies with the buffer. In Tris and the presence of sodium, taurine increases the affinity of the low affinity binding, but decreases the maximal binding of calcium. In the absence of sodium, taurine decreases affinity of the low affinity binding without altering the maximal binding. These effects on low affinity binding, however, are absent in physiological buffers representative of extracellular conditions. In buffers representative of intracellular ionic conditions, taurine increases the high affinity binding of calcium to sarcolemma in a dose-dependent manner. These results suggest that taurine exerts its cardiotonic actions through a modulation of the high affinity calcium binding on the internal aspect of the sarcolemma. Membrane phospholipids are important calcium-binding molecules in cardiac sarcolemma. Heterogeneous vesicles containing phospholipids in a ratio approximating that of rat heart sarcolemma bind significant quantities of calcium. Taurine increases calcium binding to the artificial liposomes in a manner similar to that observed for sarcolemma. Taurine also increases calcium binding to homogeneous vesicles of phosphatidylserine, but not phosphatidylinositol, phosphatidylcholine or phosphatidylethanolamine. Taurine modulation of calcium may not involve a classical protein-ligand interaction, but, instead, a low affinity attraction to sarcolemmal phospholipids. Taurine binds to sarcolemma with low affinity and positive cooperativity at concentrations normally present in the rat heart. Neither β-alanine nor guanidinoethane sulfonate, inhibitors of taurine transport, affect taurine binding. However, hypotaurine and various cations reduce binding. Heterogeneous phospholipid vesicles also bind taurine with positive cooperativity which was enhanced by the inclusion of cholesterol. Taurine associates with homogeneous vesicles of phosphatidylcholine, phosphatidylserine, or phosphatidylethanolamine. Phosphatidylinositol bind little taurine. These studies support the hypothesis that taurine exerts its modulation of sarcolemmal function through an interaction with membrane phospholipids.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectTaurine.en_US
dc.subjectSarcolemma.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.identifier.proquest8727936en_US
dc.identifier.oclc699823422en_US
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