ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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112 citing papers in PubMed.
- Local targeted suppression of neocortical spreading depolarization amplitude by viral expression of KCa3.1 channels.Gene therapy · 2026Article
- Temporal multi-omic exploration of the ventral tegmental area in chronic pain and passive coping behaviors.iScience · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Robust activity-dependent mitochondrial calcium dynamics at the AIS is dispensable for action potential generation.The Journal of physiology · 2026Article
- Kcnq2 R213 knock-in mice reveal variant- and region-specific mechanisms underlying self-limited familial neonatal-infantile epilepsy and early infantile developmental and epileptic encephalopathy.Acta neuropathologica communications · 2026Article
- Mislocalization of KCNQ2 Channels as a Pathogenic Mechanism in KCNQ2 Developmental and Epileptic Encephalopathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Cytoskeletal scaffolding of NaCurrent opinion in cell biology · 2025Review
- Psychedelics Reverse the Polarity of Long-Term Synaptic Plasticity in Cortical-Projecting Claustrum Neurons.eNeuro · 2025Article
- Persistent Na+ current couples spreading depolarization to seizures in Scn8a gain-of-function mice.Brain : a journal of neurology · 2025Article
- Biophysical properties of the membrane influence spike initiation dynamics and neuronal excitability: a focus on Kv1 channels in myelinated axons.Proceedings. Biological sciences · 2025Review
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Targeting Kv7 Potassium Channels for Epilepsy.CNS drugs · 2025Review
- Article
- An evolutionarily conserved AnkyrinG-dependent motif clusters axonal K2P K+ channels.The Journal of cell biology · 2024Article
- An ankyrin G-binding motif mediates TRAAK periodic localization at axon initial segments of hippocampal pyramidal neurons.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Plural molecular and cellular mechanisms of pore domainbioRxiv : the preprint server for biology · 2024Article
- Glycine-induced activation of GPR158 increases the intrinsic excitability of medium spiny neurons in the nucleus accumbens.Cellular and molecular life sciences : CMLS · 2024Article
- Ion Channel and Transporter Involvement in Chemotherapy-Induced Peripheral Neurotoxicity.International journal of molecular sciences · 2024Review
- Pathogenic gating pore current conducted by autism-related mutations in the NaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Phox2b-expressing neurons contribute to breathing problems in Kcnq2 loss- and gain-of-function encephalopathy models.Nature communications · 2023Article
52 more citing papers are in PubMed but not listed here.
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Abstract
Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.
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