STRUCTURAL DETERMINANTS OF DYADIC JUNCTIONS

摘要

Since Stern (4) proposed the "local control" models of cardiac excitation-contraction coupling 17 years ago, significant progress have been made on the characterization of local Ca~(2+) events, demonstration of functional coupling of L-type Ca~(2+) channels and ryanodine receptors, measurement of microdomain Ca~(2+) fluxes, modeling of Ca~(2+) dynamics in the dyadic junctions, as well as the detection of coupling defects in cardiac hypertrophy and heart failure. These advances are outlined clearly by Fowler and Smith in this Viewpoint article. However, the molecular determinants supporting the micro-architecture of dyadic junctions have not been discussed. Takeshima et al. identified junctophilins (JH) as a class of proteins spanning the membrane of junctional sarcoplasmic reticulum (jSR) and interacting with t-tubular membrane. Junctophilin-2 (JH-2) knockout mice showed deficiency in cardiac junctional complexes, disrupted Ca~(2+) transients, and embryonic lethality.