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Co-expression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.

Chia-Yi Huang, Dachen Chu, Wei-Chao Hwang, Meei-Ling Tsaur

, 2012 Apr 2 , ,

Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels comprise the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in 9 axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K(+) channel Kv3.4 in both pioneer axons and early follower axons, and L-type Ca(2+) channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were co-localized with markers of pioneer neurons and pioneer axons, such as Deleted in Colorectal Cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding, but were down-regulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1 and Kv3.3) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca(2+) -dependent electrical activity of pioneer axons and play important roles during axon pathfinding. J. Comp. Neurol., 2012. © 2012 Wiley-Liss, Inc.