Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8474945 | Journal of Molecular and Cellular Cardiology | 2014 | 11 Pages |
Abstract
Excitation-contraction coupling in cardiomyocytes requires Ca2 + influx through dihydropyridine receptors in the sarcolemma, which gates Ca2 + release through sarcoplasmic ryanodine receptors (RyRs). Ca2 + influx, release and diffusion produce a cytosolic Ca2 + transient. Here, we investigated the relationship between Ca2 + transients and the spatial arrangement of the sarcolemma including the transverse tubular system (t-system). To accomplish this, we studied isolated ventricular myocytes of rabbit, which exhibit a heterogeneously distributed t-system. We developed protocols for fluorescent labeling and triggered two-dimensional confocal microscopic imaging with high spatiotemporal resolution. From sequences of microscopic images, we measured maximal upstroke velocities and onset times of local Ca2 + transients together with their distance from the sarcolemma. Analyses indicate that not only sarcolemmal release sites, but also those that are within 1 μm of the sarcolemma actively release Ca2 +. Our data also suggest that release does not occur at sites further than 2.5 μm from the sarcolemma. The experimental data are in agreement with results from a mathematical model of Ca2 + release and diffusion. Our findings can be explained by a modified local control model, which constrains the region of regenerative activation of non-junctional RyR clusters. We believe that this model will be useful for describing excitation-contraction coupling in cardiac myocytes with a sparse t-system, which includes those from diseased heart tissue as well as atrial myocytes of some species.
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Authors
Natalia S. Torres, Frank B. Sachse, Leighton T. Izu, Joshua I. Goldhaber, Kenneth W. Spitzer, John H. Bridge,