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K Ca 2 channel localization and regulation in the axon initial segment
Author(s) -
Abiraman Krithika,
Tzingounis Anastasios V.,
Lykotrafitis George
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700605r
Subject(s) - chemistry , soma , axon , biophysics , neuroscience , potassium channel , axon hillock , membrane potential , sk channel , bk channel , ion channel , biology , biochemistry , receptor
Small conductance calcium‐activated potassium (K Ca 2) 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 K Ca 2 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 K Ca 2 channels–predominantly the K Ca 2.3 subtype–are indeed present on the AIS. We also report that cAMP‐PKA controls the axonal K Ca 2 channel surface expression. Surprisingly, and in contrast to K Ca 2 channels that were observed in the soma and dendrites, the inhibition of cAMP‐PKA increased the surface expression of K Ca 2 channels without promoting nanoclustering. Lastly, we found that axonal K Ca 2 channels seem to undergo endocytosis in a dynamin‐independent manner, unlike K Ca 2 channels in the soma and dendrites. Together, these novel results demonstrate that the distribution and membrane recycling of K Ca 2 channels differs among various neuronal subcompartments.— Abiraman, K., Tzingounis, A. V., Lykotrafitis, G. KCa2 channel localization and regulation in the axon initial segment. FASEB J. 32, 1794–1805 (2018). www.fasebj.org