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The structure of excitation-contraction coupling in atrial cardiomyocytes

Standard local control theory, which describes Ca²⁺ release during excitation-contraction coupling (ECC), assumes that all Ryanodine Receptor (RyR) complexes are equivalent. Recent data from our laboratory has called this assumption into question. Specifically, we have shown that RyR complexes in ventricular myocytes differ depending on their location within the cell. This, and other data, has led us to hypothesize that similar differences occur within the rat atrial cell.
To test this hypothesis, we have triple-labeled enzymatically-isolated, fixed myocytes to examine the distribution and colocalization of RyR, calsequestrin (CSQ), voltage-gated Ca²⁺ channels (Cav1.2), sodium-calcium exchangers (NCX), and caveolin-3 (cav-3). All images were acquired on a wide-field microscope, deconvolved, and subject to extensive analysis, including a novel method of measuring statistical significance of the recorded colocalization values.
Overall, eight surface RyR populations were identified, depending on its binding partners. One of these groups, in which RyR, Cav1.2, and NCX colocalize, may provide the structural basis for ‘eager’ sites of Ca²⁺ release in atria, while other groups were defined based on their association with cav-3, and are therefore highly likely to be under the influence of other signaling molecules located within caveolae. Importantly, although a small portion of the surface RyR in atria do colocalize with NCX alone, the majority are tightly linked to Cav1.2 alone or Cav1.2 and NCX together. Therefore, it appears likely that Cav1.2-mediated calcium-induced calcium release (CICR) is the primary method of initiating Ca²⁺ release from the SR during EC coupling.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU./3981
Date05 1900
CreatorsSchulson, Meredith Nicole
PublisherUniversity of British Columbia
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Format2681442 bytes, application/pdf

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