Review
Cell Biology
Juan Jose Garrido
Summary: Brain channelopathies are neurological disorders caused by genetic mutations that affect ion channels in the brain. These specialized proteins control the electrical activity of nerve cells, and when they do not function properly, they can lead to a range of neurological symptoms. This review focuses on how alterations in the structure, plasticity, and composition of the axon initial segment (AIS) can result in changes in action potentials and neuronal dysfunction, leading to brain diseases.
Article
Cell Biology
Piyush Bhardwaj, Don Kulasiri, Sandhya Samarasinghe
Summary: The presence of high-density AIS protein voltage-gated sodium channels (Nav) at the axon initial segment (AIS) region is crucial for action potential initiation. Computational experiments suggest that Nav channels with all serine sites available for phosphorylation bind to AnkG with strong affinity, and the concentration of Nav channels reduces significantly at low initial concentrations of AnkG and casein kinase 2, highlighting the importance of these proteins in Nav channel recruitment.
NEURAL REGENERATION RESEARCH
(2021)
Article
Neurosciences
Anna M. Lipkin, Margaret M. Cunniff, Perry W. E. Spratt, Stefan M. Lemke, Kevin J. Bender
Summary: The study revealed that in mouse layer 5 prefrontal pyramidal neurons, calcium channels were distributed differently, with Ca(V)3 channels leading to high-spot calcium influx in specific regions, while Ca(V)2 channels localized to non-hotspot areas.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Luiza Filipis, Laila Ananda Blomer, Jerome Montnach, Gildas Loussouarn, Michel De Waard, Marco Canepari
Summary: In neocortical layer-5 pyramidal neurons, the action potential (AP) generation depends on the activation of voltage-gated Na+ channels (Na(v)1.2 and Na(v)1.6) in the axon initial segment (AIS). However, the functional differences between these channels are still not well understood. This study demonstrates that Na(v)1.2 plays an exclusive role in shaping the AP by activating BK Ca2+-activated K+ channels (CAKCs) in the distal part of the AIS. The exclusive role of Na(v)1.2 reported here is important for understanding neuronal excitability.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Neurosciences
Xuanyuan Wu, Haixiang Li, Jiechang Huang, Mengqi Xu, Cheng Xiao, Shuijin He
Summary: COUP-TFI is a crucial regulator of AIS diameter in both developing and adult mouse neocortex, influencing changes in AIS diameter and impairment of AP generation. Overexpression of COUP-TFI increases AIS diameter and facilitates AP generation, but weakens the receiving spontaneous network.
NEUROSCIENCE BULLETIN
(2022)
Article
Neurosciences
Luiza Filipis, Marco Canepari
Summary: **This study presents the first optical measurement of Na+ currents in the axon initial segment (AIS) of pyramidal neurons in the somatosensory cortex, demonstrating the ability to track the kinetics of Na+ current during action potential generation more effectively. The results also show a correlation between the kinetics of Na+ current at different distances from the soma and the somatic action potential. Additionally, comparison with computer simulations of NEURON models revealed the potential of this approach in estimating the native behavior of Na+ channels accurately.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Neurosciences
H. S. Jorgensen, D. B. Jensen, K. P. Dimintiyanova, V. S. Bonnevie, A. Hedegaard, J. Lehnhoff, M. Moldovan, L. Grondahl, C. F. Meehan
Summary: Studies have shown deficits in repetitive firing in G93A SOD1 mice but not in presymptomatic G127X SOD1 mice. Immunohistochemistry for the Na+ channel Nav1.6 revealed an increase in AIS length in G127X SOD1 mice at symptom onset, leading to a faster rise in AIS components of antidromic action potentials.
Article
Multidisciplinary Sciences
Aurelie Fekete, Norbert Ankri, Romain Brette, Dominique Debanne
Summary: The distal shift of the axon initial segment (AIS) position increases axial resistance and excitability in L-5 pyramidal neurons, resulting in a decrease in the voltage threshold of the somatic action potential.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biology
Li Chen, Zhenzhen Song, Xiaowan Cao, Mingsong Fan, Yan Zhou, Guoying Zhang
Summary: The study suggests that IL-33 may be involved in the initiation of labor in human uterine smooth muscle cells by inducing endoplasmic reticulum stress through calcium influx.
Review
Biochemistry & Molecular Biology
Esben M. Quistgaard, Josephine Dannerso Nissen, Sean Hansen, Poul Nissen
Summary: The axon initial segment (AIS) plays a crucial role in neuronal signaling by initiating action potentials. Recent research has identified the proteins and molecular architecture of AIS, providing insights for future structural characterization. More studies are needed to explore the complex higher-order assemblies and improve structure predictions.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Neurosciences
Victoria Gonzalez Sabater, Mark Rigby, Juan Burrone
Summary: In this study, the initiation and propagation of action potentials (APs) along the axon were investigated using genetically encoded voltage indicators (GEVIs) in dissociated hippocampal neurons from rat embryos. It was found that APs became sharper and exhibited greater fidelity as they traveled towards distal axonal domains. Blocking voltage-gated potassium channels (K-v) resulted in an increase in AP width, especially in distal locations, suggesting that higher levels of Kv channel activity in distal axons contribute to maintaining AP fidelity.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Israt Jahan, Ryota Adachi, Ryo Egawa, Haruka Nomura, Hiroshi Kuba
Summary: This study reveals that microtubule reorganization via activation of CDK5 plays a role in the plasticity of the axon initial segment (AIS). Treatment with a high-K+ medium shortened the AIS, specifically in neurons tuned to high-frequency sound. CDK5/p35-mediated AIS shortening is achieved by promoting disassembly of microtubules at distal AIS.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Zoology
Zhi-Ya Chen, Luxin Peng, Mengdi Zhao, Yu Li, Mochizuki Takahiko, Louis Tao, Peng Zou, Yan Zhang
Summary: Action potentials (APs) in neurons are generated at the axon initial segment (AIS). We studied AP initiation and propagation in hippocampal neurons from Sprague-Dawley (SD) rats and C57BL/6 (C57) mice. Our data showed that APs traveled bidirectionally in neurons from both species, with different speeds for forward-propagating APs (fpAPs) and backpropagating APs (bpAPs). Compared with rat neurons, mouse neurons exhibited higher bpAP speed and lower fpAP speed, more distally located ankyrin G (AnkG) in AIS, and longer Nav1.2 lengths in AIS. Our findings suggest that hippocampal neurons in SD rats and C57 mice may have different AP propagation speeds, different AnkG and Nav1.2 patterns in the AIS, and different AIS plasticity properties, indicating that comparisons between these species must be carefully considered.
ZOOLOGICAL RESEARCH
(2022)
Article
Cell Biology
Yuki Ogawa, Matthew N. Rasband
Summary: The study found that the anti-Ranbp2 antibody used previously is not specific for Ranbp2. Experimental results showed that endogenously expressed Ranbp2 is not found at the AIS, but an exogenously expressed N-terminal fragment of Ranbp2 can localize at the AIS and interact with stable microtubules.
JOURNAL OF CELL SCIENCE
(2021)
Article
Neurosciences
Wei Zhang, Maria Ciorraga, Pablo Mendez, Diana Retana, Norah Boumedine-Guignon, Beatriz Achon, Michael Russier, Dominique Debanne, Juan Jose Garrido
Summary: The axon initial segment (AIS) is crucial for neuronal function, with the actin and microtubule cytoskeleton playing a key role in regulating AIS structure and function, and formins playing a critical role in maintaining AIS composition and stability.
MOLECULAR NEUROBIOLOGY
(2021)