Evidence for saltatory conduction in peripheral myelinated nerve fibres

Huxley, Andrew; Stämpfli, R.

doi:10.1113/jphysiol.1949.sp004335

Cited by 581 publications

(260 citation statements)

References 12 publications

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“…For each somatic action potential, a voltage transient occurred in the axon. The initial deflection was positive, consistent with the predicted voltage signal from action potentials recorded through the myelin at internodes (Huxley and Stämpfli, 1949;Zhou and Chiu, 2001). Axonal signals were accepted as representative of propagating action potentials if withdrawal of the axonal recording pipette by a few micrometers resulted in a loss of spike-like deflections, and if the putative axonal spikes had a relatively constant latency with respect to each somatic action potential.…”

Section: Resultsmentioning

confidence: 69%

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

2005

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In cerebellar Purkinje neurons, the reliability of propagation of high-frequency simple spikes and spikelets of complex spikes is likely to regulate inhibition of Purkinje target neurons. To test the extent to which a one-to-one correspondence exists between somatic and axonal spikes, we made dual somatic and axonal recordings from Purkinje neurons in mouse cerebellar slices. Somatic action potentials were recorded with a whole-cell pipette, and the corresponding axonal signals were recorded extracellularly with a loose-patch pipette. Propagation of spontaneous and evoked simple spikes was highly reliable. At somatic firing rates of ϳ200 spikes/sec, Ͻ10% of spikes failed to propagate, with failures becoming more frequent only at maximal somatic firing rates (ϳ260 spikes/sec). Complex spikes were elicited by climbing fiber stimulation, and their somatic waveforms were modulated by tonic current injection, as well as by paired stimulation to depress the underlying EPSCs. Across conditions, the mean number of propagating action potentials remained just above two spikes per climbing fiber stimulation, but the instantaneous frequency of the propagating spikes changed, from ϳ375 Hz during somatic hyperpolarizations that silenced spontaneous firing to ϳ150 Hz during spontaneous activity. The probability of propagation of individual spikelets could be described quantitatively as a saturating function of spikelet amplitude, rate of rise, or preceding interspike interval. The results suggest that ion channels of Purkinje axons are adapted to produce extremely short refractory periods and that brief bursts of forward-propagating action potentials generated by complex spikes may contribute transiently to inhibition of postsynaptic neurons.

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Section: Resultsmentioning

confidence: 69%

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

2005

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“…Although the function of the myelin sheath in saltatory conduction (Huxley and Stämpfli, 1949) and important details of its structure (Geren, 1954) have long been known, the molecular mechanisms of its formation have remained elusive. With this report, we established a novel role for ROCK, a key effector of Rho, in myelin sheath formation by Schwann cells.…”

Section: Discussionmentioning

confidence: 99%

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Melendez‐Vasquez

Einheber²,

Salzer³

2004

J. Neurosci.

108

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The myelin sheath forms by the spiral wrapping of a glial membrane around an axon. The mechanisms involved are poorly understood but are likely to involve coordinated changes in the glial cell cytoskeleton. Because of its key role as a regulator of the cytoskeleton, we investigated the role of Rho kinase (ROCK), a major downstream effector of Rho, in Schwann cell morphology, differentiation, and myelination. Pharmacologic inhibition of ROCK activity results in loss of microvilli and stress fibers in Schwann cell cultures and strikingly aberrant myelination in Schwann cell-neuron cocultures; there was no effect on Schwann cell proliferation or differentiation. Treated Schwann cells branch aberrantly and form multiple, small, independent myelin segments along the length of axons, each with associated nodes and paranodes. This organization partially resembles myelin formed by oligodendrocytes rather than the single long myelin sheath characteristic of Schwann cells. ROCK regulates myosin light chain phosphorylation, which is robustly, but transiently, activated at the onset of myelination. These results support a key role of Rho through its effector ROCK in coordinating the movement of the glial membrane around the axon at the onset of myelination via regulation of myosin phosphorylation and actomyosin assembly. They also indicate that the molecular machinery that promotes the wrapping of the glial membrane sheath around the axon is distributed along the entire length of the internode.

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“…The number of experimental studies is also limited. 40,63 Given the importance of ion dynamics in the vicinity of membranes in many biological phenomena, starting from action potentials in nerve cells 64,65 and ranging from cell energetics 66 to ion-mediated signaling between active membrane proteins, [67][68][69] the lack of computational studies on ion dynamics is rather surprising.…”

Section: Introductionmentioning

confidence: 99%

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

et al. 2009

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Positively charged lipid bilayer systems are a promising class of nonviral vectors for safe and efficient gene and drug delivery. Detailed understanding of these systems is therefore not only of fundamental but also of practical biomedical interest. Here, we study bilayers comprising a binary mixture of cationic dimyristoyltrimethylammoniumpropane (DMTAP) and zwitterionic (neutral) dimyristoylphosphatidylcholine (DMPC) lipids. Using atomistic molecular dynamics simulations, we address the effects of bilayer composition (cationic to zwitterionic lipid fraction) and of NaCl electrolyte concentration on the dynamical properties of these cationic lipid bilayer systems. We find that, despite the fact that DMPCs form complexes via Na + ions that bind to the lipid carbonyl oxygens, NaCl concentration has a rather minute effect on lipid diffusion. We also find the dynamics of Cl -and Na + ions at the water-membrane interface to differ qualitatively. Cl -ions have well-defined characteristic residence times of nanosecond scale. In contrast, the binding of Na + ions to the carbonyl region appears to lack a characteristic time scale, as the residence time distributions displayed power-law features. As to lateral dynamics, the diffusion of Na + ions within the water-membrane interface consists of two qualitatively different modes of motion: very slow diffusion when ions are bound to DMPC, punctuated by fast rapid jumps when detached from the lipids. Overall, the prolonged dynamics of the Na + ions are concluded to be interesting for the physics of the whole membrane, especially considering its interaction dynamics with charged macromolecular surfaces.

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Evidence for saltatory conduction in peripheral myelinated nerve fibres

Cited by 581 publications

References 12 publications

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

Axonal Propagation of Simple and Complex Spikes in Cerebellar Purkinje Neurons

Rho Kinase Regulates Schwann Cell Myelination and Formation of Associated Axonal Domains

Ion Dynamics in Cationic Lipid Bilayer Systems in Saline Solutions

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