A nanodomain is a nanometer-sized cluster of proteins found in a cell membrane. They are associated with the signal which occurs when a single calcium ion channel opens on a cell membrane, allowing an influx of calcium ions (Ca2+) which extend in a plume a few tens of nanometres from the channel pore.[1] In a nanodomain, the coupling distance, that is, the distance between the calcium-binding proteins which sense the calcium, and the calcium channel, is very small, less than 100 nm (3.9×10−6 in), which allows rapid signalling.[2] The formation of a nanodomain signal is virtually instantaneous following the opening of the calcium channel, as calcium ions move rapidly into the cell along a steep concentration gradient.[3] The nanodomain signal collapses just as quickly when the calcium channel closes, as the ions rapidly diffuse away from the pore.[3] Formation of a nanodomain signal requires the influx of only approximately 1000 calcium ions.[4]

Coupling distances greater than 100 nm (3.9×10−6 in), mediated by a larger number of channels, are referred to as microdomains.[2] nanodomain


Nanodomain signals are thought to improve the temporal precision of fast exocytosis of vesicles due to two specific properties:[5]

  • The peak concentration of calcium ions will be reached incredibly quick (within a microsecond) and maintained as long as the channel is open.
  • Closure of the channel leads to a rapid collapse of the domain due to lateral diffusion away from the pore (the site of entry). The lateral diffusion of microdomains additionally depends on the action of fast endogenous buffers (which remove the calcium and transport it away from the active zone).

Single channels are able to cause vesicular release, however, the cooperativity of different calcium channels is synapse-specific. The release driven by a single calcium ion channel minimizes the total calcium ion influx, overlapping domains can provide greater reliability and temporal fidelity.[5]


  1. ^ Wang, Lu-Yang; Augustine, George J. (26 January 2015). "Presynaptic nanodomains: a tale of two synapses". Frontiers in Cellular Neuroscience. 8: 455. doi:10.3389/fncel.2014.00455. PMC 4306312. PMID 25674049.
  2. ^ a b Eggermann, Emmanuel; Bucurenciu, Iancu; Goswami, Sarit Pati; Jonas, Peter (20 December 2011). "Nanodomain coupling between Ca2+ channels and sensors of exocytosis at fast mammalian synapses". Nature Reviews. Neuroscience. 13 (1): 7–21. doi:10.1038/nrn3125. PMC 3617475. PMID 22183436.
  3. ^ a b Stanley, Elise F. (March 2016). "The nanophysiology of fast transmitter release". Trends in Neurosciences. 39 (3): 183–197. doi:10.1016/j.tins.2016.01.005. PMID 26896416. 
  4. ^ Filadi, Riccardo; Basso, Emy; Lefkimmiatis, Konstantinos; Pozzan, Tullio (2017). "Beyond intracellular signaling: The ins and outs of second messengers microdomains nano technology". Advances in Experimental Medicine and Biology. 981: 279–322. doi:10.1007/978-3-319-55858-5_12. ISBN 9783319558585. PMID 29594866.
  5. ^ a b Oheim, Martin; Kirchhoff, Frank; Stühmer, Walter (2006). "Calcium microdomains in regulated exocytosis". Cell Calcium. 40 (5–6): 423–39. doi:10.1016/j.ceca.2006.08.007. PMID 17067670.