Activity-Dependent Modulation of Axonal Excitability in Unmyelinated Peripheral Rat Nerve Fibers by the 5-HT(3) Serotonin Receptor

2006 ◽  
Vol 96 (6) ◽  
pp. 2963-2971 ◽  
Author(s):  
Philip M. Lang ◽  
Gila Moalem-Taylor ◽  
David J. Tracey ◽  
Hugh Bostock ◽  
Peter Grafe
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Serotonin Receptor ◽  
Nerve Fibers ◽  
Nerve Trunk ◽  
Axonal Membrane ◽  
Membrane Hyperpolarization ◽  
Axonal Excitability ◽  
Activity Dependent

Activity-dependent fluctuations in axonal excitability and changes in interspike intervals modify the conduction of trains of action potentials in unmyelinated peripheral nerve fibers. During inflammation of a nerve trunk, long stretches of axons are exposed to inflammatory mediators such as 5-hydroxytryptamine [5-HT]. In the present study, we have tested the effects of m-chlorophenylbiguanide (mCPBG), an agonist at the 5-HT(3) serotonin receptor, on activity- and potential-dependent variations in membrane threshold and conduction velocity of unmyelinated C-fiber axons of isolated rat sural nerve segments. The increase in axonal excitability during application of mCPBG was much stronger at higher frequencies of action potentials and/or during axonal membrane hyperpolarization. The effects on the postspike recovery cycle also depended on the rate of stimulation. At an action potential frequency of 1 Hz or in hyperpolarized axons, mCPBG produced a loss of superexcitability. In contrast, at 0.33 Hz, a small increase in the postspike subexcitability was observed. Similar effects on excitability changes were found when latency instead of threshold was recorded, but only at higher action potential frequencies: at 1.8 Hz, mCPBG increased conduction velocity and reduced postspike supernormality. The latter effect would increase the interspike interval if pairs of action potentials were conducted along several cm in an inflamed nerve trunk. These data indicate that activation of axonal 5-HT(3) receptors not only enhances membrane excitability but also modulates action potential trains in unmyelinated, including nociceptive, nerve fibers at high impulse rates.

Strength-duration and activity-dependent excitability properties of frog afferent axons and their intraspinal projections

1991 ◽  
Vol 65 (3) ◽  
pp. 468-476 ◽  
Author(s):  
N. C. Tkacs ◽  
R. D. Wurster
Keyword(s):  
Conduction Velocity ◽  
Action Potentials ◽  
Conditioning Stimulus ◽  
Membrane Properties ◽  
Stimulation Site ◽  
Antidromic Activation ◽  
Entry Zone ◽  
Activity Dependent ◽  
Fiber Action

1. Excitability properties of afferent axons and terminal regions in frog dorsal roots (DR) and spinal cords in vitro were investigated by antidromic activation from three sites--the root, the entry zone (dorsal white matter or DW), and deep within the dorsal horn (DH)--while recordings were made from the DR. 2. Two approaches were used to assess physiological differences between telodendria and trunk axons. Rheobases and strength-duration time constants (tau sd) of single DR fibers were measured by stimulation in the DH or in the DW. Conduction velocity was estimated on the basis of onset latencies of evoked spikes (the time from stimulation to action potential arrival at the recording electrodes). Population supernormality was evaluated on the basis of responses to conditioned and unconditioned submaximal stimuli delivered to the DH or to the proximal end of isolated DRs. 3. Single-fiber action potentials occurred at longer latencies after DH stimulation than after DW stimulation. Estimated intraspinal conduction velocity was congruent to 0.6 m/s. Extraspinal conduction velocity in these fibers averaged 22.2 m/s. Average tau sd was longer in the DH than in the DW (670 microseconds vs. 204 microseconds). 4. DH and DR test responses evoked 10-150 ms after a conditioning stimulus had increased areas relative to unconditioned test responses. Conditioning-associated changes in evoked responses were greater with the DH stimulation site than with the DR stimulation site, and these changes were not altered by treatment designed to block synaptic transmission. 5. We conclude that membrane properties determining tau sd differ between large afferent axons and fine terminal regions of those axons.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals The Myelin Sheath Maintains the Spatiotemporal Fidelity of Action Potentials by Eliminating the Effect of Quantum Tunneling of Potassium Ions through the Closed Channels of the Neuronal Membrane

2019 ◽  
Vol 1 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Abdallah Barjas Qaswal
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Myelin Sheath ◽  
Quantum Tunneling ◽  
Action Potentials ◽  
Quantum Physics ◽  
Demyelinating Diseases ◽  
Neuronal Membrane ◽  
Potassium Ions ◽  
Axonal Membrane

The myelin sheath facilitates action potential conduction along the axons, however, the mechanism by which myelin maintains the spatiotemporal fidelity and limits the hyperexcitability among myelinated neurons requires further investigation. Therefore, in this study, the model of quantum tunneling of potassium ions through the closed channels is used to explore this function of myelin. According to the present calculations, when an unmyelinated neuron fires, there is a probability of 9.15 × 10 − 4 that it will induce an action potential in other unmyelinated neurons, and this probability varies according to the type of channels involved, the channels density in the axonal membrane, and the surface area available for tunneling. The myelin sheath forms a thick barrier that covers the potassium channels and prevents ions from tunneling through them to induce action potential. Hence, it confines the action potentials spatiotemporally and limits the hyperexcitability. On the other hand, lack of myelin, as in unmyelinated neurons or demyelinating diseases, exposes potassium channels to tunneling by potassium ions and induces the action potential. This approach gives different perspectives to look at the interaction between neurons and explains how quantum physics might play a role in the actions occurring in the nervous system.

Computer Model for Action Potential Propagation Through Branch Point in Myelinated Nerves

2001 ◽  
Vol 85 (1) ◽  
pp. 197-210 ◽  
Author(s):  
Lei Zhou ◽  
Shing Yan Chiu
Keyword(s):  
Action Potential ◽  
Branch Point ◽  
Myelin Sheath ◽  
Nerve Fibers ◽  
Myelinated Nerve ◽  
Axonal Membrane ◽  
Pass Filter ◽  
Low Pass Filter ◽  
Action Potential Propagation ◽  
Periaxonal Space

A mathematical model is developed for simulation of action potential propagation through a single branch point of a myelinated nerve fiber with a parent branch bifurcating into two identical daughter branches. This model is based on a previously published multi-layer compartmental model for single unbranched myelinated nerve fibers. Essential modifications were made to couple both daughter branches to the parent branch. There are two major features in this model. First, the model could incorporate detailed geometrical parameters for the myelin sheath and the axon, accomplished by dividing both structures into many segments. Second, each segment has two layers, the myelin sheath and the axonal membrane, allowing voltages of intra-axonal space and periaxonal space to be calculated separately. In this model, K ion concentration in the periaxonal space is dynamically linked to the activity of axonal fast K channels underneath the myelin in the paranodal region. Our model demonstrates that the branch point acts like a low-pass filter, blocking high-frequency transmission from the parent to the daughter branches. Theoretical analysis showed that the cutoff frequency for transmission through the branch point is determined by temperature, local K ion accumulation, width of the periaxonal space, and internodal lengths at the vicinity of the branch point. Our result is consistent with empirical findings of irregular spacing of nodes of Ranvier at axon abors, suggesting that branch points of myelinated axons play important roles in signal integration in an axonal tree.

The Ionic Basis of Axonal Conduction in the Central Nervous System of Viviparus Contectus (Millet) (Gastropoda: Prosobranchia)

1972 ◽  
Vol 57 (1) ◽  
pp. 41-53
Author(s):  
D. B. SATTELLE
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Action Potentials ◽  
Slow Component ◽  
Choline Chloride ◽  
Slight Reduction ◽  
Action Current ◽  
Sodium Dependent ◽  
Dependent Mechanism ◽  
Normal Ringer

1. The compound action potential recorded from the pleural-supraintestinal connective of Viviparus contectus consists of a large, slow component with an average conduction velocity of about 0.02 m/sec (at 23° C) and a faster component with a conduction velocity of 0.10 m/sec (at 23° C) for the fastest fibres. 2. Both fast and slow action potentials are rapidly abolished by the substitution of tris chloride and choline chloride for the sodium salts of normal Ringer. Tetrodotoxin, applied at 10-5M rapidly abolishes action potentials in all fibres. It is, therefore, concluded that a largely sodium-dependent mechanism of spike generation operates in all axons of the connective. 3. Lithium ions effectively substitute for sodium ions in maintaining the fast action potentials for extended periods, whereas tetraethylammonium ions do not. 4. When the calcium chloride of normal Ringer is replaced by sucrose, magnesium chloride or barium chloride, conduction of fast action potentials is maintained. A small increase in the sensitivity of all axons to tetrodotoxin is observed in calcium-free Ringer; a slight reduction in the spike amplitude of fast action potentials follows the application of manganous ions at 5 mM/l in normal Ringer. It is concluded that any possible contribution of calcium to the generation of the action current of the fast action potential is very small compared to that of sodium. 5. All axons of the connective function for extended periods in sodium-free (dextran) Ringer. Under these conditions, tetrodotoxin blocks conduction in all fibres at concentrations of 10-6M, suggesting that function in dextran Ringer is maintained by a sodium-dependent mechanism.

Activity-dependent sensory signal processing in mechanically responsive slowly conducting meningeal afferents

2014 ◽  
Vol 112 (12) ◽  
pp. 3077-3085 ◽  
Author(s):  
Michael Uebner ◽  
Richard W. Carr ◽  
Karl Messlinger ◽  
Roberto De Col
Keyword(s):  
Action Potential ◽  
Conduction Velocity ◽  
Receptive Fields ◽  
Low Frequency ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Action Potential Firing ◽  
Afferent Fibers ◽  
Custom Made ◽  
Activity Dependent

Activity-dependent processes in slowly conducting afferents have been shown to modulate conduction and receptive properties, but it is not known how the frequency of action potential firing determines the responses of such fibers to mechanical stimulation. We examined the responses of slowly conducting meningeal afferents to mechanical stimuli and the influence of preceding action potential activity. In hemisected rat heads with adhering cranial dura mater, recordings were made from meningeal nerves. Dural receptive fields of mechanically sensitive afferent fibers were stimulated with a custom-made electromechanostimulator. Sinusoidal mechanical stimuli of different stimulus durations and amplitudes were applied to produce either high-frequency (phasic) or low-frequency (tonic) discharges. Most fibers showed slowing of their axonal conduction velocity on electrically evoked activity at ≥2 Hz. In this state, the peak firing frequency of phasic responses to a 250-ms mechanical stimulus was significantly reduced compared with control. In contrast, the frequency of tonic responses induced by mechanical stimuli of >500 ms did not change. In a rare subtype of afferents, which showed conduction velocity speeding during activity, an increase in the phasic responses to mechanical stimuli was observed. Depending on the axonal properties of the afferent fibers, encoding of phasic components of mechanical stimuli is altered according to the immediate firing history. Preceding activity in mechanoreceptors slowing their conduction velocity seems to provide a form of low-pass filtering of action potential discharges predominantly reducing the phasic component. This may improve discrimination between harmless and potentially harmful mechanical stimuli in normal tissue.

Function of the Hyperpolarization-Activated Inward Rectification in Nonmyelinated Peripheral Rat and Human Axons

1997 ◽  
Vol 77 (1) ◽  
pp. 421-426 ◽  
Author(s):  
Peter Grafe ◽  
Stefan Quasthoff ◽  
Julian Grosskreutz ◽  
Christian Alzheimer
Keyword(s):  
Action Potential ◽  
Sural Nerve ◽  
Nerve Fibers ◽  
Stimulation Frequency ◽  
Time Dependent ◽  
Inward Rectification ◽  
Organ Bath ◽  
Vagus Nerves ◽  
Membrane Hyperpolarization ◽  
Threshold Electrotonus

Grafe, Peter, Stefan Quasthoff, Julian Grosskreutz, and Christian Alzheimer. Function of the hyperpolarization-activated inward rectification in nonmyelinated peripheral rat and human axons. J. Neurophysiol. 77: 421–426, 1997. The function of time-dependent, hyperpolarization-activated inward rectification was analyzed on compound potentials of nonmyelinated axons in the mammalian peripheral nervous system. Isolated rat vagus nerves and fascicles of biopsied human sural nerve were tested in a three-chambered, Vaseline-gap organ bath at 37°C. Inward rectification was assessed by recording the effects of long-lasting hyperpolarizing currents on electrical excitability with the use of the method of threshold electrotonus (program QTRAC, copyright Institute of Neurology, London, UK) and by measuring activity-dependent changes in conduction velocity and membrane potential. Prominent time-dependent, cesium-sensitive inward rectification was revealed in rat vagus and human sural nerve by recording threshold electrotonus to 200-ms hyperpolarizing current pulses. A slowing of compound action potential conduction was observed during a gradual increase in the stimulation frequency from 0.1 to 3 Hz. Above a stimulation frequency of 0.3 Hz, this slowing of conduction was enhanced during bath application of 1 mM cesium. Cesium did not alter action potential waveforms during stimulation at frequencies <1 Hz. Cesium-induced slowing in action potential conduction was correlated with membrane hyperpolarization. The hyperpolarization by cesium was stronger during higher stimulation frequencies and small in unstimulated nerves. These data show that a cesium-sensitive, time-dependent inward rectification in peripheral rat and human nonmyelinated nerve fibers limits the slowing in conduction seen in such axons at action potential frequencies higher than ∼0.3 Hz.

scholarly journals Some Effects of Calcium Ions on the Action Potential of Single Nodes of Ranvier

1964 ◽  
Vol 48 (1) ◽  
pp. 113-127 ◽  
Author(s):  
Werner Ulbricht
Keyword(s):  
Action Potential ◽  
Calcium Ions ◽  
Refractory Period ◽  
Qualitative Agreement ◽  
Action Potentials ◽  
Outward Current ◽  
Nerve Fibers ◽  
Current Pulses ◽  
Delayed Rectification ◽  
Voltage Clamp Analysis

Action potentials of single frog nerve fibers were recorded with the air-gap method in "low Ca" (0.26 mM) and "high Ca" (4.2 mM) solutions and compared to spikes in normal Ringer's (1.05 mM Ca). On increasing (Ca)o the action potentials became shorter, the "knee" during the falling phase as well as the threshold for abolition moved to internal potentials more positive, and the spike recovery during the relative refractory period was faster. Outward current pulses applied during an action potential affected its configuration more in low Ca than in high Ca. The onset of the delayed rectification (in the absence of Na) was found faster in high Ga. After-potentials during anelectrotonus declined more rapidly in high Ca than in low Ca. The results are compared primarily with the voltage-clamp analysis of Ca effects on squid axons and satisfactory qualitative agreement is reached.

scholarly journals The mechanosensitive ion channel TRAAK is localized to the mammalian node of Ranvier

2019 ◽  
Author(s):  
Stephen G. Brohawn ◽  
Weiwei Wang ◽  
Jürgen R. Schwarz ◽  
Annie Handler ◽  
Ernest B. Campbell ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Polyclonal Antibodies ◽  
Node Of Ranvier ◽  
Nerve Fibers ◽  
Resting Membrane Potential ◽  
Myelinated Nerve ◽  
Myelinated Nerve Fibers ◽  
Behavioral Studies ◽  
Mechanosensitive Ion Channel

ABSTRACTTRAAK is a membrane tension-activated K+ channel that has been associated through behavioral studies to mechanical nociception. We used specific monoclonal antibodies in mice to show that TRAAK is localized exclusively to nodes of Ranvier, the action potential propagating elements of myelinated nerve fibers. Approximately 80 percent of myelinated nerve fibers throughout the central and peripheral nervous system contain TRAAK in an all-nodes or no-nodes per axon fashion. TRAAK is not observed at the axon initial segment where action potentials are first generated. We used polyclonal antibodies, the TRAAK inhibitor RU2 and node clamp amplifiers to demonstrate the presence and functional properties of TRAAK in rat nerve fibers. TRAAK contributes to the ‘leak’ K+ current in mammalian nerve fiber conduction by hyperpolarizing the resting membrane potential, thereby increasing Na+ channel availability for action potential propagation. Mechanical gating in TRAAK might serve a neuroprotective role by counteracting mechanically-induced ectopic action potentials. Alternatively, TRAAK may open in response to mechanical forces in the nodal membrane associated with depolarization during saltatory conduction and thereby contribute to repolarization of the node for subsequent spikes.

Jittery Trains Induced by Synaptic-Like Currents in Cerebellar Inhibitory Interneurons

2002 ◽  
Vol 87 (1) ◽  
pp. 149-156 ◽  
Author(s):  
Puah Mann-Metzer ◽  
Yosef Yarom
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Spike Timing ◽  
Temporal Coding ◽  
Parallel Fiber ◽  
Delayed Rectifier ◽  
Inhibitory Interneurons ◽  
Synaptic Current ◽  
Large Variability ◽  
Membrane Hyperpolarization

Cerebellar inhibitory interneurons respond to parallel fiber input with a characteristic train of action potentials. Here we show that the characteristics of these trains reflect the intrinsic properties of the interneurons. In in vitro cerebellar slices, the response of these neurons to synaptic-like current resembles their in vivo response to parallel fiber input—a train of action potentials characterized by a gradual increase in interspike interval and spike amplitude. A large variability in spike timing, or jitter, was observed, the last action potential emerging from a slow depolarizing wave that lasted beyond the synaptic current and was prevented by either TTX or membrane hyperpolarization. While response duration was weakly dependent on current intensity, the variability of the overall duration was closely related to the variability of the timing of the last action potential. Blocking the Ca2+ currents or partial blockade of the delayed rectifier (TEA 2 mM) decreased the excitability, leading to a decrease in the duration and variability of the response and increasing its dependence on stimulus intensity. Increased duration and variability was observed in the presence of Cs+ ions (5 mM) that blocked an h-like current. We conclude that a persistent Na+ current governs the duration of the response, whereas the synaptic current and the spiking mechanism shape its pattern. The large variability between trials is due to the stochastic nature of the persistent Na+ current. Thus unless precise timing is achieved by a network of interconnected neurons, these results vote against temporal coding as a player in the cerebellar computational processing.

scholarly journals Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors

2014 ◽  
Vol 111 (9) ◽  
pp. 1721-1735 ◽  
Author(s):  
Jenny Tigerholm ◽  
Marcus E. Petersson ◽  
Otilia Obreja ◽  
Angelika Lampert ◽  
Richard Carr ◽  
...  
Keyword(s):  
Action Potential ◽  
Small Diameter ◽  
Axonal Membrane ◽  
Axonal Conduction ◽  
C Fibers ◽  
Experimental Approaches ◽  
Action Potential Initiation ◽  
Activity Dependence ◽  
Activity Dependent

Action potential initiation and conduction along peripheral axons is a dynamic process that displays pronounced activity dependence. In patients with neuropathic pain, differences in the modulation of axonal conduction velocity by activity suggest that this property may provide insight into some of the pathomechanisms. To date, direct recordings of axonal membrane potential have been hampered by the small diameter of the fibers. We have therefore adopted an alternative approach to examine the basis of activity-dependent changes in axonal conduction by constructing a comprehensive mathematical model of human cutaneous C-fibers. Our model reproduced axonal spike propagation at a velocity of 0.69 m/s commensurate with recordings from human C-nociceptors. Activity-dependent slowing (ADS) of axonal propagation velocity was adequately simulated by the model. Interestingly, the property most readily associated with ADS was an increase in the concentration of intra-axonal sodium. This affected the driving potential of sodium currents, thereby producing latency changes comparable to those observed for experimental ADS. The model also adequately reproduced post-action potential excitability changes (i.e., recovery cycles) observed in vivo. We performed a series of control experiments replicating blockade of particular ion channels as well as changing temperature and extracellular ion concentrations. In the absence of direct experimental approaches, the model allows specific hypotheses to be formulated regarding the mechanisms underlying activity-dependent changes in C-fiber conduction. Because ADS might functionally act as a negative feedback to limit trains of nociceptor activity, we envisage that identifying its mechanisms may also direct efforts aimed at alleviating neuronal hyperexcitability in pain patients.

Sign in / Sign up

Export Citation Format

Share Document