The electrical heterogeneity of the heart has been recognized as an important feature of normal cardiac function. In cardiac myocytes, considerable electrophysiological differences in sodium channel currents have been reported between the atria and the ventricle. Although, these differences have been primarily attributed to heterogeneous populations of Na+ channel isoforms within cardiac tissue, the link between these electrophysiological differences and certain cardiac pathologies has been loosely studied. We sought to further elucidate the electrophysiological differences between the atria and the ventricle by characterizing INa in both cell types. For these studies we had initially predicted the atria to contain a greater density of TTX-sensitive Na+ channel isoforms compared to that of the ventricle. We used two well-known Na+ channel blockers: lidocaine (100 μM, 30 μM, 10 μM) and tetrodotoxin (TTX; 10 nM, 30 nM). In addition, we also applied hydrogen peroxide (H2O2; 100 μM, 30 μM, 10 μM) to atrial myocytes, which served as our pathological model for reactive oxygen species (ROS). When we applied lidocaine to cardiac myocytes, we observed an overall mixed response in both cell types. Specifically, we noted the most significant differences (p < 0.05) in peak INa, shifts in steady-state inactivation, and impaired recovery from fast inactivation in the presence of 100 μM lidocaine. Given the non-uniform responses to lidocaine, our results support the theory that tissue specific populations of Na+ channel isoforms exist within cardiac myocytes. In order to further elucidate the electrophysiological differences between the ventricle and the atria, we applied TTX, which is selective for TTX-sensitive Na+ currents. Our results indicated no overall significant differences between the ventricle and the atria, suggesting that the population of TTX-sensitive Na+ channel isoforms within the atria specifically, may not be pharmacologically detectable. Finally, our results also demonstrated that the atria are sensitive to ROS, where H2O2 significantly prolonged the action potential duration (APD) in atrial myocytes. Our results also suggest that, in addition to INa, other ion channels may be mediating a component of the H2O2-induced prolongation of the APD in adult rat atrial myocytes. / Thesis (Master, Physiology) -- Queen's University, 2010-08-27 10:04:19.043
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/5997 |
| Date | 27 August 2010 |
| Creators | SCHLER, SARAH |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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