K _Ca 2 channel localization and regulation in the axon initial segment

Abstract

Small conductance calcium-activated potassium (K2) channels are expressed throughout the CNS and play a critical role in synaptic and neuronal excitability. K2 channels have a somatodendritic distribution with their highest expression in distal dendrites. It is unclear whether K2 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 K2 channels-predominantly the K2.3 subtype-are indeed present on the AIS. We also report that cAMP-PKA controls the axonal K2 channel surface expression. Surprisingly, and in contrast to K2 channels that were observed in the soma and dendrites, the inhibition of cAMP-PKA increased the surface expression of K2 channels without promoting nanoclustering. Lastly, we found that axonal K2 channels seem to undergo endocytosis in a dynamin-independent manner, unlike K2 channels in the soma and dendrites. Together, these novel results demonstrate that the distribution and membrane recycling of K2 channels differs among various neuronal subcompartments.-Abiraman, K., Tzingounis, A. V., Lykotrafitis, G. K2 channel localization and regulation in the axon initial segment.

Altered Expression of Ion Channels in White Matter Lesions of Progressive Multiple Sclerosis: What Do We Know About Their Function?

“…SK3 channels are found on dendrites and AIS (Abiraman et al, 2018 ). They play a role in AP propagation and regulation of neuronal excitability (Stocker, 2004 ).…”

Subcellular control of membrane excitability in the axon

“…Furthermore, activating post-synaptic muscarinic acetylcholine receptors enhanced the activity of Cav3.2 in hippocampal granule cells, resulting in Kv7 inhibition and decreased spike threshold [39]. Ca 2+ entry through AIS NMDA receptors during increased activity results in Nav and Kv7 endocytosis [40] and along with other Ca 2+ sources may also activate SK channels recently observed at the AIS of hippocampal neurons [41]. Finally, dopamine can inhibit Cav3 at the AIS of cartwheel cells, lowering excitability and suppressing burst output [42] (Summary in Figure 2b).…”

Cerebellar Golgi cell models predict dendritic processing and mechanisms of synaptic plasticity

“…As in other central neurons, like Purkinje cells [ 28 , 36 ], inferior olivary cells [ 37 ], pyramidal neurons [ 30 , 31 , 38 ]], in Golgi cells the dendritic calcium channels played a fundamental role. A variety of Ca channels were located in the dendrites [ 14 ] and AIS [ 23 , 39 ]. The models showed that, in basal dendrites, Cav2.2 channel activation followed the action potential trajectory generating rapid Ca transients.…”