Rat Sciatic Nerve Fibers Research Articles

Oxaliplatin-induced Hyperexcitation of Rat Sciatic Nerve Fibers: An Intra-axonal Study

Oxaliplatin is an agent that is used extensively in gastrointestinal cancer chemotherapy. The agent's major dose-limiting toxicity is peripheral neuropathy that can manifest as a chronic or an acute syndrome. Oxaliplatin-induced acute neuropathy is purportedly caused by an alteration of the biophysical properties of voltage-gated sodium channels. However, sodium channel blockers have not been successful at preventing acute neuropathy in the clinical setting. We report intra-axonal recordings from the isolated rat sciatic nerve preparation under the effect of oxaliplatin. The depolarization phase of single action potentials remains intact with a duration of 0.52 ± 0.02 ms (n=68) before and 0.55 ± 0.01 ms (n=68) after 1-5 h of exposure to 150 μM oxaliplatin (unpaired t-test, P > 0.05) whereas there is a significant broadening of the repolarization phase (2.16 ± 0.10 ms, n=68, before and 5.90 ± 0.32 ms after, n=68, unpaired t-test, P < 0.05). Apart from changes in spike shape, oxaliplatin also had drastic concentration- and time-dependent effects on the firing responses of fibers to short stimuli. In the intra-axonal recordings, three groups of firing patterns were indentified. The first group shows bursting (internal frequency 90 - 130 Hz, n=88), the second shows a characteristic plateau (at -19.27�2.84 mV, n=31, with durations ranging from 45 - 140 ms depending on the exposure time), and the third combines a plateau and a bursting period. Our results implicate the voltage-gated potassium channels as additional oxaliplatin targets, opening up new perspectives for the pharmacological prevention of peripheral neuropathy.

F‐actin distribution at nodes of Ranvier and Schmidt‐Lanterman incisures in mammalian sciatic nerves

Very little is known about the function of the F-actin cytoskeleton in the regeneration and pathology of peripheral nerve fibers. The actin cytoskeleton has been associated with maintenance of tissue structure, transmission of traction and contraction forces, and an involvement in cell motility. Therefore, the state of the actin cytoskeleton strongly influences the mechanical properties of cells and intracellular transport therein. In this work, we analyze the distribution of F-actin at Schmidt-Lanterman Incisures (SLI) and nodes of Ranvier (NR) domains in normal, regenerating and pathologic Trembler J (TrJ/+) sciatic nerve fibers, of rats and mice. F-actin was quantified and it was found increased in TrJ/+, both in SLI and NR. However, SLI and NR of regenerating rat sciatic nerve did not show significant differences in F-actin, as compared with normal nerves. Cytochalasin-D and Latrunculin-A were used to disrupt the F-actin network in normal and regenerating rat sciatic nerve fibers. Both drugs disrupt F-actin, but in different ways. Cytochalasin-D did not disrupt Schwann cell (SC) F-actin at the NR. Latrunculin-A did not disrupt F-actin at the boundary region between SC and axon at the NR domain. We surmise that the rearrangement of F-actin in neurological disorders, as presented here, is an important feature of TrJ/+ pathology as a Charcot-Marie-Tooth (CMT) model.

The Effect of Tramadol on the Rat Sciatic Nerve Conduction: A Numerical Analysis and Conduction Velocity Distribution Study

The aim of this study was to document the effect of tramadol as an opioid on individual fibers of rat sciatic nerve. To accomplish this objective, compound action potentials (CAPs) were recorded from isolated nerves treated with tramadol from five different concentration levels. Then recorded CAPs and the control group were analyzed by numerical methods namely Conduction Velocity Distribution (CVD) and Fast Fourier Transform (FFT). The results show that the area under CAP and the time derivative of CAP curves decreases, and the excitability of the nerve trunk falls as well (rheobase and chronaxie increases) with increasing tramadol concentration. CVD deduced by model study was divided into subgroups as SLOW (8-26 m/s), MODERATE (26-44 m/s), MEDIUM (44-60 m/s) and FAST (60-78 m/s). The decrement in percentage relative contribution of these conduction velocity groups starts with a concentration of 0.25 mM tramadol, especially in the subgroup named FAST. The power spectrum shifts from higher frequency region to lower frequency region as the tramadol concentration increases. These findings show that fast conducting fibers are more susceptible to tramadol than medium and moderate groups and tramadol possibly acts on channel activity rather than passive properties (such as space and time constant) of nerve fibers.

Selenium induced changes on rat sciatic nervefibers: Compound action potentials

The nervous system, through its important role as a communication network, governs reactions to stimuli, processes information and generates elaborate patterns of signals to control complex behaviors. Although selenium (Se) was shown to have some beneficial effects in pathological conditions, it is still a toxic element with a fairly small therapeutic window. In this study, the direct effects of Se ranging from 10(-8) to 10(-4) M were tested on rat sciatic nerve preparations. The toxicity started at 10(-8) M and the degree of alterations was found to be dose-dependent. In between the measured parameters, total compound action potential area (Astart = 3.70 +/- 0.16 ms x mV and A(-8) M = 3.04 +/- 0.14 ms x mV) and maximum depolarization points (MDstart = 6.70 +/- 0.22 mV and MD(-8) M = 6.04 +/- 0.18 mV) were the first to be affected from 10(-8) M. Latencies and conduction velocity distribution measurements have shown that nerve fibers having intermediate conduction velocities (20-35 m/s) are the first to be affected from this toxicity. Despite the fact that the new claims concluded the positive effects of the administrations, it is evident that the dose of supplementation must be fine-tuned to avoid possible side effects.

Coenzyme Q(10) and alpha-lipoic acid supplementation in diabetic rats: Conduction velocity distributions

Diabetic neuropathies are a family of nerve disorders caused by diabetes. Patients with diabetes can develop nerve problems at any time, but the longer a person has diabetes the greater the risk. This study aims to investigate diabetes- and coenzyme Q(10) (CoQ(10)) or alpha-lipoic acid (ALA) supplementation-induced changes in the conduction velocity (CV) distributions of rat sciatic nerve fibers. Sciatic nerve compound action potentials (CAPs) were recorded by suction electrode and CV distributions by the collision technique. Diabetes resulted in a significant increase in time to peak, rheobase and chronaxie values of these CAP waveforms, whereas the maximum depolarization, area, kinetics and CVs of both fast and slow nerve fiber groups were found to be decreased. Coenzyme Q(10) (CoQ(10)) supplementation was found to have some positive effect on the diabetes-induced alterations. CoQ(10) supplementation induced positive changes mainly in the area and fall-down phase of the kinetics of CAP waveforms, as well as rheobase, chronaxie and speed of the intermediately conducting groups ( approximately or equal to 40 m/s). alpha-Lipoic acid (ALA) supplementation did not produce statistically significant effects. This study has shown for the first time that diabetes induces a shift of actively contributing nerve fibers toward slower CVs, and supplementation with CoQ(10) not only stopped this shift but also tended to restore velocities toward those of the age-matched control group. In addition to its effects on mitochondrial alterations, these positive effects of CoQ10 on diabetic neuropathy can be attributed to its antioxidant activity.

In vitro assessment of the neurotoxic and neuroprotective effects of N-acetyl- l-cysteine (NAC) on the rat sciatic nerve fibers

N-acetyl- l-cysteine (NAC), at a concentration of 1–60 mM, has been previously used extensively for protection in a variety of cell cultures against the deleterious effects of various compounds. The results of this in vitro study show that NAC has certain unusual effects on the evoked compound action potential (CAP) of the rat sciatic nerve fibers. Firstly, at concentrations of 5.0, 3.5 and 2.5 mM, concentrations used by others as a protectant for cell cultures, NAC inhibits the action potentials of the sciatic nerve fibers completely in a concentration-dependent manner within a few minutes or hours (2.5 mM). Secondly, the acute inhibitory action of NAC on the CAP of the nerve fibers was not spontaneously reversible, but as soon as NAC was replaced with saline there was a partial (∼75%) recovery in the function of the nerve fibers. Thirdly, the no observed effect concentration for NAC was estimated to be 1 mM. The paradox is that NAC at 1 mM not only had no effect on the nerve fibers, but it became an excellent neuroprotective compound, giving almost 100% neuroprotection against cadmium-induced neurotoxicity. The results show a possible effect of NAC on voltage-gated sodium and potassium channels. The observed neuroprotective-neurotoxic properties of NAC require careful reconsideration of its use in either in vitro studies or in vivo pharmaceutical applications.

SEXUAL DEPENDENCY OF RAT SCIATIC NERVE FIBER CONDUCTION VELOCITY DISTRIBUTIONS

Gender differences, either with the structural or through with hormones, dictate how the corresponding organ or organ system responses to physiological signals. Current study aims to investigate gender dependent differences in conduction related parameters of rat sciatic nerve. Compound action potentials (CAP) were recorded via suction electrode whereas the conduction velocity distributions (CVD) were performed using the method known as collision technique in the literature. Studied CAP parameters, namely conduction velocities (CV), area of the CAPs and time required to reach the maximum depolarization (TP) have been found significantly different for female and male rats. Detailed analyses have shown that sex dependent differences were more remarkable in the right leg responses of female and male rats. Additionally, CVDs indicate that the number of fibers having CVs between 5–30 m/s is much more in male right sciatic nerve trunk when compared to age matched female rats. The present study, for the first time clearly shows that shift in the contribution of nerve fibers to lower CVs is the main causal of the sex dependent differences seen in rat sciatic nerve fibers.

Dexamethasone decreases blood flow in normal nerves and dorsal root ganglia.

An experimental physiologic and histologic study of dexamethasone effects on peripheral nerves. To characterize the effect of topically applied 0.4% dexamethasone on acute changes in nerve blood flow and subsequent histologic changes in rat sciatic nerve fibers. Dexamethasone is an anti-inflammatory glucocorticoid used clinically to reduce the neural consequences of inflammation. Several reports of accidental injury to nerves after steroid injections have raised questions about the mechanisms involved in dexamethasone-induced neurotoxic injury. Nerve blood flow studies using a laser Doppler flowmeter were conducted in animals with stable temperature and arterial pressure. Dexamethasone 0.4%, 0.1 mL was applied topically to rat sciatic nerve in the following protocol groups: 1) nerve blood flow recording every 5 minutes for 30 minutes, and 2) initial nerve blood flow recording and repeat recording at 4 hours. Three additional animals had 30-minute nerve blood flow recordings in which normal saline was substituted for dexamethasone; these animals were used for control and to assure that the experimental preparation was viable throughout the observational period. Additional groups of two animals each received dexamethasone but were used only for neuropathologic observation at 2, 4, and 6 days after treatment. Neuropathologic studies were conducted on glutaraldehyde-fixed, plastic-embedded tissue. Application of saline to the exposed sciatic nerves did not significantly change nerve blood flow from baseline values. Nerve blood flow values remained constant throughout the observational period. Dexamethasone, however, significantly reduced nerve blood flow in both the 30-minute and 4-hour groups. Some animals showed an initial transient increase in blood flow before nerve blood flow began to steadily decline to the final values reported. Neuropathologic changes were minimal and consisted only of edema and occasional subperineurial activation of Schwann cells. No demyelination or degeneration was seen. Dexamethasone causes statistically significant reductions in normal nerve blood flow at 30 minutes and 4 hours after topical application; however, the reduction is on average below the threshold for causing ischemic changes in the structure of peripheral nerve fibers.

The delayed effect of cortagen on the restoration of injured nerve function.

It is known that fragments of large peptide molecules affect the growth, development, and regeneration of nerve tissue [1‐3, 5, 9]. The existence of biologically active short peptides allows obtaining their artificial analogues that can stimulate regeneration of injured peripheral nerve fibers. One of these newly synthesized peptides is the tetrapeptide cortagen (Ala-Glu-AspPro), which was obtained using targeted construction based on the amino acid analysis of cortexin, a polypeptide preparation possessing neurotrophic activity. Earlier, we showed that cortagen stimulated the growth of rat sciatic nerve fibers at the initial regeneration stages after their injury [6]. Of special interest are late regeneration stages, when the degree of reinnervation and functional restoration of injured nerve fibers can be estimated. In this work, we performed the study five months after the nerve injury. This time is sufficient for the majority of regenerating fibers to reach the target tissues and complete myelination [7]. Sixteen male Wister rats weighing 200 to 250 g were used. The operations were performed under ketamine narcosis (intramuscular injections of ketamine and rometar (50 and 15 mg/kg, respectively)). The restoration of the sciatic-nerve function was studied after the nerve transsection and suturing its ends with an epiperineural suture [4]. To study the effect of cortagen on regeneration, the animals received intramuscular injections of the peptide (10 μ g/kg) daily for 10 days after the operation. The animals of the control group received intramuscular injections of saline according to the same scheme. The functional state of the nerve was evaluated by recording the compound action potentials in vitro according to Legrand [4]. The functional properties of the regenerating foot skin mechanoreceptors were studied by recording the impulse activity of single fibers with the use of the vaseline bridge technique on a special ebonite platform [1]. The mechanical threshold for each receptor was determined using von Frey monofilaments. The adaptive properties of the receptors were evaluated using mechanical stimulation with the trapezoid stimulus (20‐50 ms; a three-threshold amplitude). The data were statistically processed using Student’s t test. Preparation of the injured sciatic nerve for testing in vitro showed that cortagen caused a decrease in the neuroma located in the suture area. Therefore, simultaneously with measuring the conduction velocity of action potential along the regenerating fragment of the nerve that had already recovered, we also evaluated the conduction velocity through the suture site. We found that the sciatic nerve conduction velocity had, by the moment of the test, been completely restored in the animals of both groups. The method of compound action potential recording did not show the effect of cortagen on conductivity of regenerating nerve fibers. The conductivity of action potential along the distal nerve section was 23.5 ∠ 1.4 and 22.8 ∠ 1.9 m/s in the control and experimental animals, respectively. The conductivity of action potential through the suture was 22.2 ∠ 0.1 and 24.0 ∠ 2.6 m/s in the control and experimental animals, respectively. Note that the compound action potential was recorded in vitro , when standard registration conditions were provided by placing the nerve on a platform with limited interelectrode distance, which allowed determining the conductivity of action potential only along the most rapidly conducting (presumably, motor) nerve fibers classified with group A. It is known that injuries are most harmful for the sensor nerve fibers [10]. The final stage of regeneration of the injured nerve is restoration of the sensitivity of the denervated tissue. With this in mind, we studied the functional properties of foot skin mechanoreceptors (the target tissue of the sciatic nerve) and analyzed the action potentials occurring in single sensory fibers in response to foot mechanical stimulation.

Preferential block of small myelinated sensory and motor fibers by lidocaine: in vivo electrophysiology in the rat sciatic nerve.

Controversy still surrounds the differential susceptibility of nerve fibers to local anesthetics and its relation to selective functional deficits. In the current study we report features of conduction blockade in different classes of rat sciatic nerve fibers after injection of lidocaine by a percutaneous procedure that closely resembles clinical applications. In 30 adult male Sprague-Dawley rats (weight, 300-400 g) during general anesthesia, impulses were recorded in different classes of sensory axons (large, Aalpha and beta fibers; small, Adelta myelinated fibers and unmyelinated C fibers) and motor axons (large, Aalpha fibers; small, Agamma myelinated fibers) classified by conduction velocity. The sciatic nerve was stimulated distally, and impulses were recorded from small filaments teased from L4-L5 dorsal (sensory) and ventral (motor) roots sectioned acutely from the spinal cord. Lidocaine at concentration of 0.05-1% was injected percutaneously in 0.1-ml solutions at the sciatic notch. Both tonic (stimulated at 0.5 Hz) and use-dependent (stimulated at 40 Hz for Adelta and Agamma fibers and at 5 Hz for C fibers) impulse inhibitions by lidocaine were assayed. Minimal effective (threshold) lidocaine concentrations (i.e., to block conduction in 10% of fibers) were, for sensory, 0.03% for Adelta, 0.07% for Aalphabeta, and 0.09-0.1% for C fibers, and for motor, 0.03% for Agamma and 0.05% for Aalpha fibers. The order of fiber susceptibility, ranked by concentrations that gave peak tonic fiber blockade of 50% (IC50s), was Agamma > Adelta = Aalpha > Aalphabeta > C. Faster-conducting C fibers (conduction velocity > 1 m/s) were more susceptible (IC50 = 0.13%) than slower ones (conduction velocity < 1 m/s; IC50 = 0.30%). At 1% lidocaine, all fibers were tonically blocked. Use-dependent effects accounted for only a modest potentiation of block (at a lidocaine concentration of 0.25%) in Adelta and Agamma fibers, and in C fibers phasic stimulation had even smaller effects and sometimes relieved tonic block. Susceptibility to lidocaine does not strictly follow the "size principle" that smaller (slower) axons are always blocked first. This order of fiber blockade is qualitatively consistent with previous reports of the order of functional deficits in the rat after percutaneous lidocaine, that is, motor = proprioception > nociception, if we assume that motor deficits first arise from conduction failure in Agamma fibers and that nociception relies on C fiber conduction.

Sorting of Regenerating Rat Sciatic Nerve Fibers with Target-Derived Molecules

The functional outcome of microsurgical repair of divided nerves is disappointing since many regenerating axons fail to reach appropriate targets. Sorting of regenerating axons according to target tissue might be used to improve functional regeneration. The aim of the present study is to see if regenerating axons can be sorted into functionally different bundles with target-derived molecules. The proximal stump of the adult rat sciatic nerve was sutured into the inlet of a silicon Y-tube. The two branches of the Y-tube were filled with agarose primed with filtrates prepared from skin and muscle homogenates from the operated rat. The tibial and sural nerves were inserted in the two branches of the Y-tube. Six weeks later the sciatic nerve axons showed vigorous regeneration into both branches. Electron microscopic examination of regenerated nerve segments showed numerous myelinated and unmyelinated axons. The proportion of myelinated axons was significantly larger in the muscle-gel branch than in the skin-gel branch. Retrograde tracing from the nerve regenerates with Fast Blue and Fluoro-Ruby showed that ventral horn neurons at L4–L5 segmental levels were preferentially labeled from the muscle-gel branch. Neurons in corresponding dorsal root ganglia were labeled from both Y-tube branches (no significant numerical difference). A few neurons of both types contained both tracers. Measurements revealed that sensory neurons labeled from the muscle-gel branch were significantly larger (mean perikaryal area 870 μm2) than neurons labeled from the skin-gel branch (mean area 580 μm2). We conclude that regenerating motor and sensory axons can be sorted with target-derived molecules.

Conduction block by clonidine is not mediated by α2-adrenergic receptors in rat sciatic nerve fibers

Background and Objectives: Clonidine, an α2-adrenergic agonist, has been shown to prolong local anesthesia. It appears that clonidine by itself produces conduction block by acting on peripheral nerves. However, whether clonidine-induced conduction block is mediated through α2-adrenergic receptors remains unclear. The purpose of this study was to see if clonidine's nerve-blocking action was through α2-adrenergic receptors by examining clonidine's action in the presence of α2-adrenergic antagonists. Methods: The compound action potentials (CAPs) evoked by electrical stimuli were recorded from the isolated rat sciatic nerve in a recording chamber. Conduction block was examined by analyzing CAPs with regard to peak amplitude and time-to-peak in the presence of clonidine alone or clonidine plus α2-adrenergic antagonist yohimbine or idazoxan. Results: Both clonidine and yohimbine produced concentration-dependent, reversible, conduction block. Based on concentration-response relationships, the 50% of effective concentration (EC50) were estimated to be 1.61 ± 0.51 mmol/L (mean ± SD) for clonidine and 51.4 ± 27.2 μmol/L for yohimbine. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 μmol/L yohimbine produced conduction block to a level close to the mean value between conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 μmol/L yohimbine alone. Addition of idazoxan, a more specific α2-adrenergic antagonist than yohimbine, to clonidine was without effect on clonidine-induced conduction block. Conclusions: The results indicated that the mixture of clonidine and yohimbine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block was not reversed by coapplication with a specific α2-adrenergic antagonist idazoxan. These data suggest that clonidine's effects likely depend on mechanisms not mediated by α2-adrenergic receptors. Reg Anesth Pain Med 2000;25:620-625.

Conduction Block by Clonidine Is Not Mediated by α2-Adrenergic Receptors in Rat Sciatic Nerve Fibers

Conduction Block by Clonidine Is Not Mediated by α2-Adrenergic Receptors in Rat Sciatic Nerve Fibers

Morphological analysis of peripheral nerve regenerated by means of vein grafts filled with fresh skeletal muscle.

Clinical data have shown that a vein segment filled with fresh skeletal muscle can be considered a good autologous grafting conduit for the repair of peripheral nerve lesions. In this study, the long-term morphological organization of rat sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is further analysed by light and electron microscopy. Regenerated nerve fibers were organized into fascicles of various sizes that were clearly delimited by perineurial-like shells made by long and thin cytoplasmic processes of perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted skeletal muscle fibers were still detectable among nerve fiber fascicles. However, in spite of the persistence of skeletal muscle along the graft, regenerated nerve fibers showed a good morphological pattern of regeneration, providing further evidence that the muscle-vein-combined grafting technique represents an effective surgical alternative to the classical fresh nerve autograft for the repair of peripheral nerve defects.

Activity-dependent variations in conduction velocity of C fibers of rat sciatic nerve

Changes in the conduction velocity subsequent conduction block were characterized following impulse activity in single C fibers of rat sciatic nerves. C fibers which had the same resting conduction velocities often exhibited quite different profiles of the activity-dependent latency change and/or conduction block following impulses. The results imply underlying variation among C fibers in the activity-dependent excitability changes, especially in the build-up and recovery of the hypoexcitable phases.

Excitability changes in C fibers of rat sciatic nerve following impulse activity

Three phases in the oscillatory changes of both threshold and conduction velocity were identified following impulse activity in single C fibers of rat sciatic nerves. These after-oscillations, occurring after the refractory period, varied with the number and timing of preceding ‘conditioning’ impulses. The excitability changes differed both qualitatively and quantitatively among fibers, thus implying underlying variation among C fibers in the density and distribution of voltage-gated channels and ion pumps.

Changes in axonal impulse conduction correlate with sensory modality in primary afferent fibers in the rat

Conduction velocity was measured in vivo in single cutaneous afferent fibers of rat sciatic nerve that were characterized by natural stimulation. During sustained electrical stimulation, impulses slowed less and propagated more reliably in cold fibers (both Aδ and C) than in nociceptive fibers of similar conduction velocity. Velocity in cold fibers tended to stabilize after an initial decrease rather than decrease throughout the stimulation as for nociceptive fibers. The slowing correlated with axon modality and hence with natural firing pattern, raising the possibility that impulse activity can determine conduction properties of axons.

Modification of the Na-dependent action potential in myelinated fibers of rat sciatic nerve exposed to phorbol ester

Exposure of rat sciatic nerve to the active phorbol 1,2-β-myristate-13-acetate (b-PMA), but not to the inactive analogue 4-α-phorbol-12,13-didecanoate (a-PDD), is followed by a decrease of the compound action potential amplitude, rate of rise, and conduction velocity, and an increase of the threshold, and of the duration of the refractory period. The effect is concentration-dependent, the K d being 250 NM. The attenuated Na-dependent action potential is tetrodotoxin (TTX)-sensitive, but after exposure to b-PMA the sensitivity to TTX is decreased from K d = 45nM to 400nM. Action potential depression is larger when Ca is replaced by Mg (but not by Ba), or when Na is replaced by Li. The replacement of K by Cs, or exposure to potassium channel blockers such as 4-aminopyridine (4AP) and tetra-ethyl ammonium (TEA) has no effect. The results indicate that in the myelinated axons of rat sciatic nerve, exposure to b-PMA induces modification of Na channels.

The association of the supernormal period and the depolarizing afterpotential in myelinated frog and rat sciatic nerve

Excitability properties of isolated frog and rat sciatic nerve fibers were examined using intra-axonal and sucrose-gap recording techniques. Paired stimulation experiments on rat myelinated fibers indicate that a small proportion (11%; n = 84) of these axons demonstrate decreased threshold indicative of a supernormal period. In contrast, 81% ( n = 23) of frog axons displayed a supernormal period. A depolarizing afterpotential was observed in most of the rat and frog fibers having a supernormal period and the depolarizing afterpotential increased in magnitude and duration during hyperpolarization. In addition to whole nerve stimulation, a supernormal period could be induced by stimulation of a single axon via current passage through the recording microelectrode. Brief (2–5 ms) subthreshold depolarizing pulses were followed by a slowly decaying depolarization and a period of increased excitability that mimicked the supernormal period. A supernormal period was also observed in the whole nerve preparation using a sucrose-gap technique. The magnitude and duration of the supernormal period, as measured in the sucrose-gap, were greater for frog nerve than for rat nerve. Additionally, a larger postspike negativity, the extracellular equivalent of the intra-axonally observed depolarizing afterpotential, was present in sucrose-gap recordings for frog nerve than for rat nerve. The results indicate that the depolarizing afterpotential is an important determinant of the supernormal period, and that both the depolarizing afterpotential and supernormal period are more prominent in frog than in rat sciatic nerve.

Functional differences between 4-aminopyridine and tetraethylammonium-sensitive potassium channels in myelinated axons

Intracellular recordings from rat sciatic nerve fibers showed that the potassium channel blocking agents 4-aminopyridine (4-AP) and tetraethylammonium (TEA) had different effects on action potential waveform. When applied alone, TEA did not appreciably alter the waveform of an individual action potential, whereas 4-AP application resulted in action potential broadening and, in some axons, repetitive firing. A prolonged afterhyperpolarization which was blocked by TEA occurred subsequent to repetitive firing. These results indicate the presence of at least two pharmacologically defined potassium channels in mammalian peripheral nerve fibers. The 4-AP-sensitive potassium channels are important for rapid action potential repolarization and the TEA-sensitive potassium channels may serve to modulate axonal excitability during repetitive firing.