Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath.

Ritchie, J. M.; Rogart, R. B.

doi:10.1073/pnas.74.1.211

Cited by 305 publications

(154 citation statements)

References 28 publications

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“…In the internodal axonal membrane, the voltage-dependent sodium channel is found at concentrations of 20 -25 channels/m 2 , compared with concentrations ranging from 1000 channels/m 2 (Shrager, 1989) to 12,000 channels/m 2 (Ritchie and Rogart, 1977) at the node of Ranvier. The asymmetric distribution of ion channels in the myelinated axon and the regular spacing of these nodes at ϳ100 times the axonal diameter (Rushton, 1951;Chiu, 1980) are critical for the fast conduction velocities associated with these axons and represent an interesting problem in cell polarity and membrane differentiation.…”

Section: Abstract: Node Of Ranvier; Cell Adhesion Molecules; Ankyrinmentioning

confidence: 99%

Morphogenesis of the Node of Ranvier: Co-Clusters of Ankyrin and Ankyrin-Binding Integral Proteins Define Early Developmental Intermediates

1997

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Ankyrin G 480/270 kDa and three ankyrin-binding integral membrane proteins (neurofascin, NrCAM, and the voltagedependent sodium channel) colocalize within a specialized domain of the spectrin-actin network found at axonal segments of nodes of Ranvier in myelinated axons. Before myelination in embryonic nerves, ankyrin G 480/270 kDa and the related ankyrin isoform ankyrin B 440 kDa are co-expressed along with NrCAM in an abundant, continuous distribution along the length of axons. This study has resolved intermediate stages in the developmental transition from a continuous distribution of ankyrin G 480/270 kDa in all axons to a highly polarized localization at the node of Ranvier in the developing rat sciatic nerve. The first detected event is formation of clusters containing the cell adhesion molecules neurofascin and NrCAM at sites independent of myelin-associated glycoprotein (MAG)-staining Schwann cell processes. Subsequent steps involve recruitment of ankyrin G 480/270 kDa and the voltage-dependent sodium channel to cluster sites containing cell adhesion molecules, and elaboration of MAG-staining Schwann cell processes adjacent to these cluster sites. Formation of the mature node of Ranvier results from the fusion of asynchronously formed pairs of clusters associated with MAG-positive Schwann cells flanking the site of presumed node formation. Studies with the hypomyelinating mutant mouse trembler demonstrate that the elaboration of compact myelin is not required for the formation of these clustered nodal intermediates. Clustering of neurofascin and NrCAM precedes redistribution of ankyrin G 480/270 kDa and the voltage-dependent sodium channel, suggesting that the adhesion molecules define the initial site for subsequent assembly of ankyrin and the voltage-dependent sodium channel.

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Section: Abstract: Node Of Ranvier; Cell Adhesion Molecules; Ankyrinmentioning

confidence: 99%

Morphogenesis of the Node of Ranvier: Co-Clusters of Ankyrin and Ankyrin-Binding Integral Proteins Define Early Developmental Intermediates

1997

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“…The density of voltage-gated ion channels throughout the plasma membrane is finite. For example, in muscle fibres, the density of the voltage-gated sodium channels was estimated to be 380 channels per mm 2 (Almers & Levinson 1975), whereas in mammalian myelinated nerve fibres, the density of sodium channels can be as high as 12 000 per mm 2 in nodal areas and as low as 25 channels per mm 2 in internodal areas (Ritchie & Rogart 1977). Thus, a disadvantage of electrodes with small surface area is the relatively low current that can be generated by the membrane patch in contact with the electrode or the number of passive ion channels through which current can flow.…”

Section: Estimate Of the Seal Resistance Formed Bymentioning

confidence: 99%

Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices

Hai

Dormann

Shappir

et al. 2009

J. R. Soc. Interface.

137

186

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Interfacing neurons with micro-and nano-electronic devices has been a subject of intense study over the last decade. One of the major problems in assembling efficient neuroelectronic hybrid systems is the weak electrical coupling between the components. This is mainly attributed to the fundamental property of living cells to form and maintain an extracellular cleft between the plasma membrane and any substrate to which they adhere. This cleft shunts the current generated by propagating action potentials and thus reduces the signal-to-noise ratio. Reducing the cleft thickness, and thereby increasing the seal resistance formed between the neurons and the sensing surface, is thus a challenge and could improve the electrical coupling coefficient. Using electron microscopic analysis and field potential recordings, we examined here the use of gold micro-structures that mimic dendritic spines in their shape and dimensions to improve the adhesion and electrical coupling between neurons and micro-electronic devices. We found that neurons cultured on a gold-spine matrix, functionalized by a cysteine-terminated peptide with a number of RGD repeats, readily engulf the spines, forming tight apposition. The recorded field potentials of cultured Aplysia neurons are significantly larger using gold-spine electrodes in comparison with flat electrodes.

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“…On the other hand, analysis of membrane currents in demyelinated nerve fibres from alloxan diabetic rats (Brismar, 1979), in diphtheria toxin-treated nerves (Bostock, Sears & Sherratt, 1981;Brismar, 1981) or after acute myelin loosening treatments (Chiu & Ritchie, 1981 showed that K, but not Na channels are present under the internodal myelin of mammalian or amphibian nerve fibres. Interestingly, Na channels which are restricted to the nodal membrane under normal conditions (Ritchie & Rogart, 1977) appear at the internodes as a consequence of demyelination by diphtheria toxin (Bostock & Sears, 1978;Brismar, 1981;see Waxman & Foster, 1980, for review).…”

Section: Introductionmentioning

confidence: 99%

Presynaptic currents in mouse motor endings

Brigant

Mallart

1982

The Journal of Physiology

254

180

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SUMMARY1. We used external electrodes placed under precise visual control on motor endings of the mouse to record electrical activity promoted by nerve stimulation.2. Three types of wave form have been observed in relation to well-defined electrode emplacements: (i) at the transition between myelinated and non-myelinated parts of the axon, the wave form consists of two negative deflexions preceded by a small positivity (preterminal response), (ii) at the main part of the terminal branches, we obtained a two component positive wave form (terminal response) and (iii) electrode positions in a narrow area between the former and the latter yielded triphasic (positive-negative-positive) wave forms (intermediate responses).3. Since these responses could not be readily interpreted in terms of classical description of membrane currents associated with propagating action potentials, we used specific channel blocking agents to identify wave form components.4. Bath application of tetraethylammonium or aminopyridines, or, better, a combination of both, suppressed delayed positive deflexions of terminal and intermediate responses and the late negative component of preterminal responses. Local inophoretic drug application showed that K channels are present only at the terminal part of the endings. K+ outflux promotes a local circuit whose sink is located at the preterminal part where it generates the late negative deflexion of the preterminal response.5. Local application of tetrodotoxin suppressed the first negative component of preterminal responses but failed to affect electrical activity at the terminal part of the endings. This indicates that Na channels, and, therefore, action potential generation, are restricted to the preterminal part.6. Suppression of K conductance revealed a slow inward current at the terminal part of the endings which could be identified as a Ca current. Ba2+ and Sr2+ could substitute for Ca2+ as inward current carriers.7. Activation of spatially separated Na channels, on one side, and of K and Ca channels, on the other, generated ionic currents and separated local circuit currents which flow between preterminal and terminal parts (and vice versa). Thus, the signals recorded at-each point of motor endings correspond to the sum of ionic and passive currents entering (or leaving) the membrane at that point.8. The present results represent a further example of heterogeneity of axonal membrane.

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Density of sodium channels in mammalian myelinated nerve fibers and nature of the axonal membrane under the myelin sheath.

Cited by 305 publications

References 28 publications

Morphogenesis of the Node of Ranvier: Co-Clusters of Ankyrin and Ankyrin-Binding Integral Proteins Define Early Developmental Intermediates

Morphogenesis of the Node of Ranvier: Co-Clusters of Ankyrin and Ankyrin-Binding Integral Proteins Define Early Developmental Intermediates

Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices

Presynaptic currents in mouse motor endings

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