Nanodomain

What is a Nanodomain?

In molecular biology, a nanodomain, in reference to calcium signaling, is where highly localized Ca²⁺ signals associated with a single (or very few at most) ion channel(s) that extend over a few tens of nm from the channel pore.^[1] Larger signalling distances from the pore (>100 nm) mediated by a larger number of channels, are referred to as microdomains. Nanodomains are related to, but not the same as coupling distance, which explicitly refers to the distance between the calcium-binding proteins (or "sensors") that are located within a few nanometers of an open calcium channel. The coupling distance is particularly important in the temporality of pre-synaptic signalling and if Ca²⁺ influx is seen in a nanodomain then one would also expect to see tighter coupling distances in order to expose the calcium sensor to high enough concentrations of Ca²⁺ to cause vesicular exocytosis of neurotransmitters to occur.

Properties of Nanodomains

Nanodomains are thought to improve the temporal precision of fast exocytosis of vesicles due to two specific properties:^[2]

• The peak concentration of Ca²⁺ will be reached incredibly quickly (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)

It is found that single channels are able to cause vesicular release, however the cooperativity of different calcium channels is synapse specific. The release driven by a single Ca²⁺ channel minimizes the total Ca²⁺ influx, overlapping domains can provide greater reliability and temporal fidelity.^[3]

References