Nanojunctions of the Sarcoplasmic Reticulum Deliver Site- and Function-Specific Calcium Signaling in Vascular Smooth...

Vasoactive agents may induce myocyte contraction, dilation, and the switch from a contractile to a migratory-proliferative phenotype(s), which requires changes in gene expression. These processes are directed, in part, by Ca²⁺ signals, but how different Ca²⁺ signals are generated to select each function is enigmatic. We have previously proposed that the strategic positioning of Ca²⁺ pumps and release channels at membrane-membrane junctions of the sarcoplasmic reticulum (SR) demarcates cytoplasmic nanodomains, within which site- and function-specific Ca²⁺ signals arise. This chapter will describe how nanojunctions of the SR may: (1) define cytoplasmic nanospaces about the plasma membrane, mitochondria, contractile myofilaments, lysosomes, and the nucleus; (2) provide for functional segregation by restricting passive diffusion and by coordinating active ion transfer within a given nanospace via resident Ca²⁺ pumps and release channels; (3) select for contraction, relaxation, and/or changes in gene expression; and (4) facilitate the switch in myocyte phenotype through junctional reorganization. This should serve to highlight the need for further exploration of cellular nanojunctions and the mechanisms by which they operate, that will undoubtedly open up new therapeutic horizons.