Structural evidence for perinuclear calcium microdomains in cardiac myocytes

J Mol Cell Cardiol. 2011 Mar;50(3):451-9. doi: 10.1016/j.yjmcc.2010.11.021. Epub 2010 Dec 14.


At each heartbeat, cardiac myocytes are activated by a cytoplasmic Ca(2+) transient in great part due to Ca(2+) release from the sarcoplasmic reticulum via ryanodine receptors (RyRs) clustered within calcium release units (peripheral couplings/dyads). A Ca(2+) transient also occurs in the nucleoplasm, following the cytoplasmic transient with some delay. Under conditions where the InsP3 production is stimulated, these Ca(2+) transients are regulated actively, presumably by an additional release of Ca(2+) via InsP3 receptors (InsP3Rs). This raises the question whether InsP3Rs are appropriately located for this effect and whether sources of InsP3 and Ca(2+) are available for their activation. We have defined the structural basis for InsP3R activity at the nucleus, using immunolabeling for confocal microscopy and freeze-drying/shadowing, T tubule "staining" and thin sectioning for electron microscopy. By these means we establish the presence of InsP3R at the outer nuclear envelope and show a close spatial relationship between the nuclear envelope, T tubules (a likely source of InsP3) and dyads (the known source of Ca(2+)). The frequency, distribution and distance from the nucleus of T tubules and dyads appropriately establish local perinuclear Ca(2+) microdomains in cardiac myocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Calcium Signaling / physiology
  • Cell Nucleus / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Mice
  • Microscopy, Confocal / methods
  • Microscopy, Electron / methods
  • Myocytes, Cardiac / metabolism*
  • Nuclear Envelope / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum / metabolism


  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ryanodine Receptor Calcium Release Channel
  • Phosphotransferases (Alcohol Group Acceptor)
  • Inositol 1,4,5-trisphosphate 3-kinase
  • Calcium