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Advanced Neurology The AIS structure and function

APs in the AIS [2,5] . This polarized distribution may reflect technology . As a result of its ability to determine
[40]
discrete functions of Na channel subtypes in AP initiation the onset of AP, kinetic dysfunction in AIS can lead to
+
and backpropagation. neurological disorders, such as epilepsy [47-50] .
Potassium ion (K ) channels in the AIS are important Second, the AIS can “filter” molecules to separate
+
for repolarization of AP. The density of K channels in the cell body from the axon, limiting the diffusion and
+
the distal AIS is also 10-fold of that in the cell body . exchange of molecules in different parts, and maintaining
[34]
K 7.2 and K 7.3 (KCNQ2/3) channels form homomeric cell polarity [6,22,51] . Since it is located between the axon
v
v
or heteromeric complexes, which interact with AnkG and and the soma, it serves as a critical regulatory center that
[35]
gather in the AIS . Although K 1.1 and K 1.2 channels controls the proteins entering into the axon, and thus plays
v
v
do not bind to AnkG, they still cluster at the distal end a crucial role in maintaining the neuron’s polarity . Either
[52]
of the AIS by binding to the scaffold protein postsynaptic for cytoplasmic proteins or for vesicles, the AIS has been
density-93 (PSD93) [20,36] . reported to have filtering functions. There is an actin-
Calcium ion (Ca ) channels have also been reported based cytoplasmic filter that could prevent the diffusion
2+
in the AIS . Previous study has shown that Ca channels of soluble macromolecules larger than 13 nm. This has
2+
[17]
may be modulated by dopaminergic signaling . Unlike been proposed as a mechanism for regulating cytoplasmic
[37]
Na and K channels in the AIS, very little is known about protein movement [53,54] . Within the AIS, studies have shown
+
+
the molecular mechanisms of Ca channels. different trafficking pathways in vesicles carrying axonal or
2+
dendritic protein. For instance, vesicles containing axonal
There is usually only one axon in a neuron. The so-called proteins are preferentially trafficked into the axon . On
[55]
somatic axon grows from the cell body through a short axon the other hand, the trafficking of vesicles carrying dendritic
hillock. However, in cultured neurons, approximately 20% proteins is stopped in the AIS and redirected back to the
of neuronal axons grow from the dendrite, which we refer soma [55-59] .
to as dendritic axons. This type of axon has been observed
in rat pyramidal cells in previous studies [29,38,39] . According 5. Plasticity of the AIS
to a recent study, axons emanate from the basal dendritic
arbor in more than half of all CA1 pyramidal neurons and AIS plasticity refers to the adaptive responses in the nervous
30% of those in rat pups . Correspondingly, the AIS also system to change its structure and function in response to
[38]
[60,61]
has different origins. In this review, “dendritic AIS” refers neuronal activity . Ion channel compositions at the AIS
to AIS with a dendritic origin, whereas “somatic AIS” vary across different types of neurons. The differences in
refers to AIS with a somatic origin. Our previous study has AIS length and location may be the basis for the different
shown that although somatic AIS has a similar length as neuronal firing properties. For instance, retinal ganglion
dendritic AIS, the distribution of Na 1.2 was significantly cells with different visual properties have different
v
[62]
narrower in dendritic AIS . AIS lengths and locations in the axons . Despite the
[40]
importance of these differences for neuronal function, the
4. Physiological functions of the AIS mechanisms controlling AIS length and location remain
largely unknown. Recent studies have revealed that AIS
APs are initiated at the AIS. In the 1950s when the structure length or location is dynamically regulated in response
and molecular composition of the AIS were mostly to normal developmental and pathological conditions.
unknown, people speculated that the AIS or axon hillock For example, in rat cortical neurons, the length of AIS
was the AP initiation site based on intracellular recording undergoes dynamic changes during their visual system
observations [41-43] . The AIS has a lower AP threshold than development . Previous studies have investigated the
[63]
the somatodendritic domain . In an autoradiography long-term activity-dependent plasticity regulation of the
[42]
study using Na channel-binding I-scorpion toxin, it was AIS in neurons in vivo and in vitro and found that the
+
125
first revealed that Na channel density was higher at the position and length of the AIS would make corresponding
+
AIS . In recent years, more and more studies have shown [60,61,64,65]
[44]
that the AIS is the AP initiation site in different types of changes and adapt to changes in external factors .
CNS neurons [28,40,45,46] . Using quantitative freeze-fracture This phenomenon, also known as AIS plasticity, is usually
electron microscopy immunogold labeling, Lorincz et al. accompanied by alterations in neuronal excitability.
have confirmed that the concentration of Na 1.6 channels Several studies have suggested that neurons may
v
at the AIS and nodes of Ranvier is approximately 40-fold alter excitability by changing their AIS length or
higher than that at the soma in hippocampal neurons . location in response to changes in developmental and
[29]
Our previous work has also confirmed that AP is initiated pathological conditions. For example, when avian nucleus
at the distal end of the AIS through voltage imaging magnocellularis neurons are deprived of auditory inputs,
Volume 2 Issue 1 (2023) 3 https://doi.org/10.36922/an.v2i1.274