The delayed rectifier potassium current IKr (hERG) participates in repolarization of the cardiac action potential and is implicated in one form of inherited Long QT Syndrome. The goal of this study was to characterize the biophysical properties of IKr in isolated rabbit ventricular myocytes and hERG expressed in a mammalian cell line using mathematical, electrophysiological and molecular biological techniques. Incorporation of results into a mathematical gating model of IKr revealed that the current did not follow the typical Hodgkin-Huxley type gating formulation and therefore comprised a gating model paradox. Furthermore, it was found that different groups of divalent cations selectively affected specific kinetic properties of I Kr, with the relief of rectification of the current by the Cd 2+-like class of divalent cations (Cd2+, Ni 2+, Co2+ and Mn2+; mM range) and the block of the current by Zn2+ (0.1--1 mM) being the most prominent effects. The biophysical properties of hERG were found to be more sensitive to Cd2+ compared to rabbit IKr (muM as opposed to mM concentrations). The relief of rectification of native rabbit IKr and expressed human hERG by the Cd2+-like group of divalent cations and block of rabbit IKr by Zn2+ may be attributed to specific interactions with distinct sites associated with different regions of the channel.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.30722 |
| Date | January 1999 |
| Creators | Paquette, Tyna. |
| Contributors | Shrier, Alvin (advisor) |
| 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 | Master of Science (Department of Physiology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001740521, proquestno: MQ64427, Theses scanned by UMI/ProQuest. |
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