Geon 2. Microtubules at the Axon Initial Segment MT

 

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Figure 1. Molecular organization of the AIS. The AIS can be divided into three layers: the plasma membrane, submembrane coat, and inner AIS shaft (left), each having AIS-specific features (zoomed view at right). The submembrane coat consists of Ankyrin-G, βIV-spectrin, and actin filaments. Microtubules, which usually exist in the form of fascicles, are located in the inner AIS shaft. Click here to enlarge. [Source: Jones and Svitkina, 2016]

The AIS can be divided into three layers as illustrated in Figure 1. During early development, the thickness of the submembrane coat varies in the range 3–11 nm (Jones et al., 2014). From electron micrographs (Figure 2), the coat thickness is about the same as the diameter of a microtubule (25 nm). Therefore, the distance between the center of a microtubule and the middle of the membrane cannot be shorter than 40 nm. At this minimum distance, the electric field produced at the membrane by a tubulin dimer is on the same order of magnitude as the resting membrane potential field (Chapter 1). The diameter of AIS is about 1500 nm while translocation from 40 nm to 130 nm is sufficient to reduce the hyperpolarizing field from a microtubule by an order of magnitude. Thus, translocation of a microtubule within the AIS can have significant impact on channel gating. This property could play a crucial role in the excitability modulated by electromagnetic waves and ultrasound.

Microtubule Fascicles at AIS

A microtubule fascicle is a bundle of several individual microtubules that are parallel with each another and cross linked. An AIS may contain 1 - 7 fascicles and the number of microtubules in each fascicle varies between 2 and 25. Its average number depends on neuronal types. In the motor neurons of the spinal cord, the number of microtubules per fascicle ranges from three to five, but in the pyramidal neurons of the cerebral cortex, the number can reach 22. Single or isolated microtubules are rarely observed in AIS (Palay et al., 1968).

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Figure 2. The cross section of AIS for a Purkinje cell revealed by electron microscope. The submembrane coat is marked by "dl" (dense layer). The arrow indicates a microtubule fascicle which appears as beads on a linear or branched string. Each bead represents a microtubule. The fascicle indicated by the arrow 1 contains five microtubules. [Source: Palay et al., 1968]

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Figure 3. The cross section of AIS for a pyramidal neuron. [Source: Palay et al., 1968]

The bundling of microtubules into fascicles is a unique feature of the AIS. This special structure was not found in the nodes of Ranvier, even though they resembles AIS in many aspects. Since AIS is the initiation site of nerve impulses and enriched with voltage-gated ion channels, one may expect the microtubule fascicles to play a role in neuronal excitability, as already did by Palay and colleagues. In 1968, they postulated that " the regulated contraction of the microtubules could change the shape of the initial segment and thus alter the configuration of the plasmalemma in this region, and consequently its permeability, with a resultant change in excitability".

In the past few years, evidence for the involvement of microtubules in excitability was accumulating. First, neurodegenerative disorders (including Alzheimer's disease) are usually preceded by hyperexcitability and the Tau protein (a microtubule associated protein) has been demonstrated to modulate neuronal excitability (Holth et al., 2013; DeVos et al., 2013; Li et al., 2014). Second, the unique structure of AIS is well-suited for microtubules to AMPLIFY the effects of extracellular electric fields, which have received great interest in recent years because a growing body of evidence suggests that they may play a critical role in working memory and synchronization.

 

Author: Frank Lee
First published: January 16, 2017