Referenced in: none

Automatically associated channels: Kv10.1

Title: Couplons in rat atria form distinct subgroups defined by their molecular partners.

Authors: Meredith N Schulson, David R L Scriven, Patrick Fletcher, Edwin D W Moore

Journal, date & volume: J. Cell. Sci., 2011 Apr 1 , 124, 1167-74

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21385843

Abstract
Standard local control theory, which describes Ca(2+) release during excitation-contraction coupling (ECC), assumes that all ryanodine receptor 2 (RyR2) complexes are equivalent. Findings from our laboratory have called this assumption into question. Specifically, we have shown that the RyR2 complexes in ventricular myocytes are different, depending on their location within the cell. This has led us to hypothesize that similar differences occur within the rat atrial cell. To test this hypothesis, we have triple-labelled enzymatically isolated fixed myocytes to examine the distribution and colocalization of RyR2, calsequestrin (Casq), voltage-gated Ca(2+) channels (Ca(v)1.2), the sodium-calcium exchanger (Ncx) and caveolin-3 (Cav3). A number of different surface RyR2 populations were identified, and one of these groups, in which RyR2, Ca(v)1.2 and Ncx colocalized, might provide the structural basis for 'eager' sites of Ca(2+) release in atria. A small percentage of the dyads containing RyR2 and Ca(v)1.2 were colocalized with Cav3, and therefore could be influenced by the signalling molecules it anchors. The majority of the RyR2 clusters were tightly linked to Ca(v)1.2, and, whereas some were coupled to both Ca 1.2 and Ncx, none were with Ncx alone. This suggests that Ca(v)1.2-mediated Ca(2+) -induced Ca(2+) release is the primary method of ECC. The two molecules studied that were found in the interior of atrial cells, RyR2 and Casq, showed significantly less colocalization and a reduced nearest-neighbour distance in the interior, compared with the surface of the cell. These differences might result in a higher excitability for RyR2 in the interior of the cells, facilitating the spread of excitation from the periphery to the centre. We also present morphometric data for all of the molecules studied, as well as for those colocalizations found to be significant.