Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation

Hu, Wenqin; Tian, Cuiping; Li, Tun; Yang, Mingpo; Hou, Han; Shu, Yousheng

doi:10.1038/nn.2359

Cited by 635 publications

(1,029 citation statements)

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“…Consequently, a new method [1][2][3][4] has recently been developed for patch-clamp recording from the thin axons of both projection neurons and interneurons. We expect that this new method will facilitate studies on axon physiology.…”

Section: Establishment Of the Tight-seal Patch-clamp Techniquementioning

confidence: 99%

“…At the cut end, the ax- Different recording configurations can be used on the axonal blebs ( Fig. 1), including cell-attached, whole-cell, outside-out patch and giant outside-out patch recordings [1][2][3][4] .…”

Section: Axonal Bleb Recordingmentioning

confidence: 99%

“…For simultaneous recordings from the soma and axon of layer-5 pyramidal neurons in the prefrontal cortex [1][2][3][4] , whole-cell recording at the soma is first established with a patch pipette filled with an internal solution containing Regular patches can also be excised from the axonal blebs using conventional procedures (Fig. 1B).…”

Section: Axonal Bleb Recordingmentioning

confidence: 99%

“…In fact, in some experiments one may want to avoid space clamp problems and influences from the somatodendritic compartments, so isolated axonal blebs (Fig. 1B-D) are ideal preparations [1] . The isolated blebs are giant outside-out axonal patches that can be obtained by making a cut at the main axon (moving a sharp glass pipette that has been inserted into the target location) to disconnect the bleb from the main axon (Fig.…”

Section: Axonal Bleb Recordingmentioning

confidence: 99%

“…The thin structure of most axons in the central nervous system (CNS) prevents direct access of patch pipettes to the axonal membrane; therefore, it was impossible to probe the properties and functions of axonal ion channels and neurotransmitter receptors. A recently developed axonal recording method, known as the axonal bleb recording [1][2][3][4] , has been successfully used in studies on the physiology of CNS axons.…”

Section: Introductionmentioning

confidence: 99%

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Axonal bleb recording

Shu

2012

Neurosci. Bull.

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Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments. The cell body and relatively thick dendrites are the most accessible compartments of a neuron, due to their large diameters and therefore great membrane surface areas. However, axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods. Recently, a new method of patchclamp recording has been developed, enabling direct and tight-seal recording from cortical axons. These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures. This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal, the action potential, and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.

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Section: Establishment Of the Tight-seal Patch-clamp Techniquementioning

confidence: 99%

Section: Axonal Bleb Recordingmentioning

confidence: 99%

Section: Axonal Bleb Recordingmentioning

confidence: 99%

Section: Axonal Bleb Recordingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Axonal bleb recording

Shu

2012

Neurosci. Bull.

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Axon Initial Segment

Debanne

Garrido

2018

Encyclopedia of Life Sciences

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The axon initial segment (AIS) is a specialised region of the axon where the action potential is initiated following integration of excitatory and inhibitory inputs. The AIS contains high density of sodium and potassium channels anchored on scaffold proteins, but it also includes receptors to neurotransmitters and neuromodulators. Besides its role in action potential initiation, the AIS constitutes a diffusion barrier that controls cytoplasmic traffic towards the axon. Activity-dependent plasticity has been recently shown to affect the length and position of the AIS whereas stimulation of ligand-gated receptors alters the ion channel content of the AIS. Thus, the AIS represents a critical element in neuronal excitability and its plasticity.

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Functional and pharmacological evaluation of a novel SCN2A variant linked to early‐onset epilepsy

Adney

Millichap

DeKeyser

et al. 2020

Ann Clin Transl Neurol

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Objective We identified a novel de novo SCN2A variant (M1879T) associated with infantile‐onset epilepsy that responded dramatically to sodium channel blocker antiepileptic drugs. We analyzed the functional and pharmacological consequences of this variant to establish pathogenicity, and to correlate genotype with phenotype and clinical drug response. Methods The clinical and genetic features of an infant boy with epilepsy are presented. We investigated the effect of the variant using heterologously expressed recombinant human NaV1.2 channels. We performed whole‐cell patch clamp recording to determine the functional consequences and response to carbamazepine. Results The M1879T variant caused disturbances in channel inactivation including substantially depolarized voltage dependence of inactivation, slower time course of inactivation, and enhanced resurgent current that collectively represent a gain‐of‐function. Carbamazepine partially normalized the voltage dependence of inactivation and produced use‐dependent block of the variant channel at high pulsing frequencies. Carbamazepine also suppresses resurgent current conducted by M1879T channels, but this effect was explained primarily by reducing the peak transient current. Molecular modeling suggests that the M1879T variant disrupts contacts with nearby residues in the C‐terminal domain of the channel. Interpretation Our study demonstrates the value of conducting functional analyses of SCN2A variants of unknown significance to establish pathogenicity and genotype–phenotype correlations. We also show concordance of in vitro pharmacology using heterologous cells with the drug response observed clinically in a case of SCN2A‐associated epilepsy.

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Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation

Cited by 635 publications

References 49 publications

Axonal bleb recording

Axonal bleb recording

Axon Initial Segment

Functional and pharmacological evaluation of a novel SCN2A variant linked to early‐onset epilepsy

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