Cardiac conduction: a new multifactorial paradigm

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Title Cardiac conduction: a new multifactorial paradigm
Publication Type dissertation
School or College College of Engineering
Department Biomedical Engineering
Author Veeraraghavan, Rengasayee
Date 2011
Description Cardiac conduction is the phenomenon of sequential triggering of electrical action potentials and, thereby, mechanical contraction in the myocytes that make up cardiac muscle. While much has been learned about this phenomenon over the years, conduction abnormalities continue to underlie potentially lethal cardiac arrhythmias in a multitude of disease states. Further, it is also clear that conduction failure in many pathophysiological states results from multifactorial alterations to the myocardium. In the first part of this work, we demonstrate a novel role for the cardiac inward-rectifying potassium current (IK1) in determining conduction heterogeneities under normal conditions and the unmasking of regional heterogeneities in expression of the cardiac sodium channel (Nav1.5) when the cardiac sodium current (INa) is reduced. In the second part we demonstrate that pharmacological activation of repolarizing potassium currents - the ATP-sensitive potassium current (IKATP) and the slow delayed rectifier potassium current (IKs) - both slow conduction. However, these effects demonstrate different dependencies on INa availability depending on whether the potassium channel activated is inwardly-rectifying (such as Kir6.2 which carries IKATP) or voltage-gated (such as KvLQT1 which carries IKs). iv In the third part, we demonstrate a novel role for interstitial volume (VIS) in regulating anisotropic cardiac conduction and its dependence on gap junction coupling. These findings may help resolve the ongoing debate on the precise nature of the conduction velocity - gap junction relationship. Overall, this work advances the understanding of interrelationships between the determinants of cardiac conduction and their effect on conduction heterogeneities during normal as well as challenging conditions.
Type Text
Publisher University of Utah
Subject Biophysics; Cardiac Conduction; Electrical Action Potentials
Dissertation Name Doctor of Phiosophy
Language eng
Rights Management © Rengasayee Veeraraghavan
Format application/pdf
Format Medium application/pdf
ARK ark:/87278/s63v3sd3
Setname ir_etd
ID 1380617
Reference URL https://collections.lib.utah.edu/ark:/87278/s63v3sd3
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