Resolving the structural basis of cardiac excitation-contraction coupling

TL;DRAbstract

Calcium (Ca2+) induced release of Ca2+ from the sarcoplasmic reticulum (SR) triggered by voltage-dependent trans-sarcolemmal Ca2+ fluxes is thought to form the basis of excitation-contraction (EC) coupling in cardiac myocytes. Clusters of ryanodine receptors (RyR) that are responsible for this Ca2+ release are known to reside on termini of the SR (located abundantly near z-lines) that form close junctions with the sarcolemmal membrane and invaginations known as t-tubules. Sarcolemma and t-tubules contain L-type Ca2+ channels and Na+/Ca2+ exchanger (NCX) proteins that may provide effective Ca2+ trigger currents if placed close to junctional RyRs. Using a novel protocol of immunofluorescence confocal microscopy, the architecture of SR and t-tubules in rat ventricular myocytes has been visualized at a resolution that was previously not achieved with optical techniques. This method revealed a subset of RyR clusters that were apparently non-junctional. Improved co-localization analysis meth

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