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Updated: Feb 18, 2026

Use of Primary Cultured Hippocampal Neurons to Study the Assembly of Axon Initial Segments
Published on: February 12, 2021
KCa2 channel localization and regulation in the axon initial segment
Krithika Abiraman1, Anastasios V Tzingounis1,2, George Lykotrafitis1,3
1Department of Biomedical Engineering, University of Connecticut, Storrs, Connecticut, USA.
Abstract:
Small conductance calcium-activated potassium (KCa2) channels are expressed throughout the CNS and play a critical role in synaptic and neuronal excitability. KCa2 channels have a somatodendritic distribution with their highest expression in distal dendrites. It is unclear whether KCa2 channels are specifically present on the axon initial segment (AIS), the site at which action potentials are initiated in neurons. Through a powerful combination of toxin pharmacology, single-molecule atomic force microscopy, and dual-color fluorescence microscopy, we report here that KCa2 channels-predominantly the KCa2.3 subtype-are indeed present on the AIS. We also report that cAMP-PKA controls the axonal KCa2 channel surface expression. Surprisingly, and in contrast to KCa2 channels that were observed in the soma and dendrites, the inhibition of cAMP-PKA increased the surface expression of KCa2 channels without promoting nanoclustering. Lastly, we found that axonal KCa2 channels seem to undergo endocytosis in a dynamin-independent manner, unlike KCa2 channels in the soma and dendrites. Together, these novel results demonstrate that the distribution and membrane recycling of KCa2 channels differs among various neuronal subcompartments.-Abiraman, K., Tzingounis, A. V., Lykotrafitis, G. KCa2 channel localization and regulation in the axon initial segment.
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