Cardiac action potential (AP) properties are not uniform because of functional specialization in different regions. The thesis of these studies was that important aspects of regional cardiac electrical function in health and disease are determined by heterogeneous ionic current expression. / The inward rectifier current, IK1, responsible for the resting membrane potential (RMP) and late repolarization, is greater in ventricle than atrium. Atrial-ventricular IKI differences result in important electrophysiological differences between atrium and ventricle. To gain insight into the mechanisms of this IK1 variation, we compared the expression and distribution of inward rectifier subunits Kir2.1/2.3, believed to underlie IK1, in both regions. Ventricles had greater Kir2.1 and lower Kir2.3 expression than atrium. The subcellular distributions of these subunits also differed between the two regions. Our findings suggest that, in addition to the intensity of subunit expression, cellular subunit location affects local channel function. / To further examine the effects of channel subunit expression and distribution on regional electrophysiology, we studied the pulmonary vein (PV) myocardial sleeve. PVs are important in atrial fibrillation (AF) initiation and maintenance and exhibit unique current profiles compared with adjacent atrial cardiomyocytes. Our findings demonstrate a greater PV expression of ERG and KvLQT1---the channel subunits that underlie the rapid and slow components of the delayed rectifier current, IK, respectively. KvLQT1 was diffusely distributed in atrial cardiomyocytes, in contrast to the transverse tubular (TT) and intercalated disk (ID) PV distribution. Kir2.3 abundance was similar in both regions, but differently distributed with a TT and ID LA distribution and ID localization in PVs. Observed expression and distribution differences between atrial and PV cardiomyocytes may account for the smaller Vmax, less negative RMP and shorter AP duration in PVs, which contribute to their arrhythmic diathesis. / The PVs are thought to act as fibrillatory foci in congestive heart failure (CHF). We compared channel subunit expression in PV cardiomyocytes from (rapid ventricular pacing induced) CHF and control hearts. CHF decreased KvLQT1 expression, increased expression of ERG and the sodium calcium exchange subunit, NCX, and altered the subcellular KvLQT1 distribution. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85584 |
| Date | January 2004 |
| Creators | Melnyk, Peter, 1975- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002198768, proquestno: AAINR12908, Theses scanned by UMI/ProQuest. |
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