Role of Voltage-Dependent K+ and Ca2+ Channels in Coronary Electromechanical Coupling: Effects of Metabolic Syndrome

dc.contributor.advisorTune, Johnathan D.
dc.contributor.authorBerwick, Zachary C.
dc.contributor.otherBasile, David P.
dc.contributor.otherMather, Kieren J.
dc.contributor.otherObukhov, Alexander G.
dc.contributor.otherSturek, Michael Stephen
dc.date.accessioned2012-10-19T14:10:11Z
dc.date.available2012-10-19T14:10:11Z
dc.date.issued2012-10-19
dc.degree.date2012en_US
dc.degree.disciplineDepartment of Cellular & Integrative Physiologyen
dc.degree.grantorIndiana Universityen_US
dc.degree.levelPh.D.en_US
dc.descriptionIndiana University-Purdue University Indianapolis (IUPUI)en_US
dc.description.abstractRegulation of coronary blood flow is a highly dynamic process that maintains the delicate balance between oxygen delivery and metabolism in order to preserve cardiac function. Evidence to date support the finding that Kv and Cav1.2 channels are critical end-effectors in modulating vasomotor tone and blood flow. Yet the role for these channels in the coronary circulation in addition to their interdependent relationship remains largely unknown. Importantly, there is a growing body of evidence that suggests obesity and its pathologic components, i.e. metabolic syndrome (MetS), may alter coronary ion channel function. Accordingly, the overall goal of this investigation was to examine the contribution coronary Kv and Cav1.2 channels to the control of coronary blood flow in response to various physiologic conditions. Findings from this study also evaluated the potential for interaction between these channels, i.e. electromechanical coupling, and the impact obesity/MetS has on this mechanism. Using a highly integrative experimental approach, results from this investigation indicate Kv and Cav1.2 channels significantly contribute to the control of coronary blood flow in response to alterations in coronary perfusion pressure, cardiac ischemia, and during increases in myocardial metabolism. In addition, we have identified that impaired functional expression and electromechanical coupling of Kv and Cav1.2 channels represents a critical mechanism underlying coronary dysfunction in the metabolic syndrome. Thus, findings from this investigation provide novel mechanistic insight into the patho-physiologic regulation of Kv and Cav1.2 channels and significantly improve our understanding of obesity-related cardiovascular disease.en_US
dc.identifier.urihttps://hdl.handle.net/1805/3017
dc.identifier.urihttp://dx.doi.org/10.7912/C2/1997
dc.language.isoenen_US
dc.subjectcoronary circulation, ion channel, blood flow, obesity, metabolic syndromeen_US
dc.subject.lcshCoronary circulationen_US
dc.subject.lcshCoronary circulation -- Regulation -- Endocrine aspectsen_US
dc.subject.lcshCoronary heart disease -- Pathophysiologyen_US
dc.subject.lcshBiochemical markersen_US
dc.subject.lcshIon channelsen_US
dc.subject.lcshBlood flowen_US
dc.subject.lcshObesityen_US
dc.subject.lcshMetabolic syndromeen_US
dc.titleRole of Voltage-Dependent K+ and Ca2+ Channels in Coronary Electromechanical Coupling: Effects of Metabolic Syndromeen_US
dc.typeThesisen
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