Clustering of voltage-gated ion channels as an evolutionary trigger of myelin formation.

Ohm H; Rey S; Klämbt C

Abstract

Neurons carry apical dendrites that perceive information and a basal axon that transmits the computed information towards its targets. The axon originates at the axon hillock which is followed by the axon initial segment. Here, action potentials are initiated that are based on millisecond long openings of specific voltage-gated sodium and potassium channels that are conserved in all parahoxozoa (Placozoa, Cnidaria, Bilateria) (Li et al., 2015). This indicates that the basic principles in action potential generation and spreading are evolutionarily conserved. The conductance velocity of action potentials likely affects the evolutionary success of any animal species as it contributes, for example, to the success of escape responses. Physical laws state that axonal transduction velocity depends on the size of the axon. Alternatively, conductance speed is gained by arranging voltage-gated ion channels in spatially separated clusters. Such a distribution is thought to be a defining feature of the vertebrate nervous system and accumulations of voltage-gated ion channels are seen at the axon initial segment and the nodes of Ranvier. Together with intervening myelin, this enables saltatory transduction, which allows very fast conduction velocities. Surprisingly, recent work demonstrated a clustered distribution of voltage-gated ion channels in the nervous system of the invertebrate Drosophila melanogaster (Rey et al., 2023). Channels are enriched at the axon initial segments of motor- and sensory neurons, cluster on a molecular scale with spacing of about 0.7 µm, supporting micro-saltatory conductance. Similar to in vertebrates, the positioning of ion channels is influenced by glia. Moreover, glia in adult flies form myelin-like structures next to the axon initial segments (Rey et al., 2023). Thus, the evolution of saltatory conductance is not specific to vertebrates but likely started before the separation of vertebrates and invertebrates.