scholarly journals Nerve Excitability Differences in Slow and Fast Motor Axons of the Rat: more than just Ih

2019 ◽  
Author(s):  
James M. Bell ◽  
Chad Lorenz ◽  
Kelvin E. Jones
Keyword(s):  
Sodium Pentobarbital ◽  
Motor Axons ◽  
Recovery Cycle ◽  
Cation Current ◽  
Nerve Excitability ◽  
Peripheral Nerve Excitability ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Inwardly Rectifying ◽  
Threshold Electrotonus

AbstractObjectiveThe objective was to determine if choice of anaesthetic confounded previous conclusions about the differences in nerve excitability indices between fast and slow motor axons.MethodologyNerve excitability of the rat sciatic nerve was tested while measuring responses of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles. The experiments were conducted with sodium pentobarbital (SP) anaesthetic and compared to previous results that used ketamine-xylazine (KX).Results and ConclusionsPrevious conclusions about the differences in nerve excitability indices between TA and SOL motor axons using KX were corroborated and extended when experiments were done with SP. Nerve excitability indices sensitive to changes in hyperpolarization-activated inwardly rectifying cation current (Ih) indicated an increase in Ih in SOL axons compared to TA axons (e.g. S3 (−100 %), t=7.949 (df=10), p < 0.0001; TEh (90–100 ms), t=2.659 (df=20), p = 0.0145; hyperpolarizing I/V slope, t=4.308 (df=19), p = 0.0004). SOL axons also had a longer strength-duration time constant (t=3.35 (df=20), p = 0.0032) and a longer and larger magnitude relative refractory period (RRP (ms) t=3.53 (df=12), p = 0.0041; Refractoriness at 2 ms t=0.0055 (df=9), p = 0.0055).Anaesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischaemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These differences have important implications for the use of nerve excitability measures during processes such as ageing where it is believed that there is a selective loss of fast axons.New & NoteworthyNerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of motor axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.

scholarly journals Nerve excitability differences in slow and fast motor axons of the rat: more than just Ih

2019 ◽  
Vol 122 (4) ◽  
pp. 1728-1734
Author(s):  
James M. Bell ◽  
Chad Lorenz ◽  
Kelvin E. Jones
Keyword(s):  
Peripheral Nerves ◽  
Motor Axons ◽  
Recovery Cycle ◽  
Nerve Excitability ◽  
Peripheral Nerve Excitability ◽  
Slow Twitch ◽  
Ischemic Depolarization ◽  
Fast Twitch ◽  
Threshold Electrotonus ◽  
Insight Into

The objective was to determine biophysical differences between fast and slow motor axons using threshold tracking and demonstrate confounds related to anesthetic. Nerve excitability of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles was tested. The experiments were conducted with pentobarbital sodium (SP) anesthetic and compared with previous results that used ketamine-xylazine (KX). Nerve excitability indices measured with SP show definitive differences between TA and SOL motor axons that extend beyond previous reports. Nerve excitability indices sensitive to changes in Ih indicated an increase in SOL axons compared with TA axons [e.g., S3 t = 7.949 (df = 10), P < 0.001; hyperpolarizing threshold electrotonus (90–100 ms), t = 2.659 (df = 20); P = 0.01; hyperpolarizing I/V slope, t = 4.308 (df = 19); P < 0.001]. SOL axons also had a longer strength-duration time constant [ t = 3.35 (df = 20); P = 0.003] and a longer and larger magnitude relative refractory period [RRP (ms) t = 3.53 (df = 12); P = 0.004; Refractoriness at 2 ms, t = 0.0055 (df = 9); P = 0.006]. Anesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These results provide empirical evidence, beyond conduction velocity, that the biophysical properties of motor axons vary with the type of muscle fiber innervated. These differences suggest that fast axons may be predisposed to dysfunction during hyperpolarizing stresses, e.g., electrogenic sodium pumping following sustained impulse conduction. NEW & NOTEWORTHY Nerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.

scholarly journals Motor axon excitability measures in the rat tail are the same awake or anaesthetized using sodium pentobarbital

2019 ◽  
Author(s):  
Kelvin E Jones ◽  
David J Bennett
Keyword(s):  
Female Rats ◽  
Sodium Pentobarbital ◽  
Test Results ◽  
Bonferroni Correction ◽  
Motor Axons ◽  
Nerve Excitability ◽  
Cord Injury ◽  
Discrete Measures ◽  
Awake Condition ◽  
Rat Tail

AbstractBackgroundNerve excitability tests in sciatic motor axons are sensitive to anaesthetic choice. Results using ketamine/xylazine (KX) are different from those using sodium pentobarbital (SP). It is not clear which results are most similar to the awake condition, though results using SP appear more similar to human results.MethodsNerve excitability in tail motor axons was tested in 8 adult female rats with a chronic sacral spinal cord injury. These animals have no behavioural response to electrical stimulation of the tail and were tested awake and then anaesthetized using SP.ResultsThe nerve excitability test results in the awake condition were indistinguishable from the results when the same rats were anaesthetized with sodium pentobarbital. Summary plots of the test results overlap within the boundaries of the standard error and paired t-tests on the 42 discrete measures generated by nerve excitability testing yielded no significant differences (after Bonferroni correction for multiple comparisons).ConclusionsNerve excitability test results in rat motor axons are the same whether the animals are awake or anesthetized using sodium pentobarbital.

Long-term persistence of enlarged motor units in partially denervated hindlimb muscles of cats

1990 ◽  
Vol 64 (4) ◽  
pp. 1261-1269 ◽  
Author(s):  
A. R. Luff ◽  
K. Torkko
Keyword(s):  
Motor Units ◽  
Contralateral Side ◽  
Cross Sectional Area ◽  
Type I ◽  
Sectional Area ◽  
Motor Axons ◽  
Cross Sectional ◽  
Single Motor Units ◽  
Slow Twitch ◽  
Fast Twitch

1. It was the aim of this study to determine the effect that regenerating motor axons would have on enlarged or sprouted motor units that had been established for a relatively long time. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After 200+ days single motor units were isolated, and their isometric contractile properties were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch-fatigable (FF), fast-twitch-fatigue-resistant (FR), and slow-twitch-fatigue-resistant (S). 3. It had been established previously that regenerating motor axons via L7 returned to the experimental muscles by approximately 100 days. Therefore from 100 to 200 days it was assumed that the sprouted units would be in competition with the regenerating axons. The extent of the original denervations was variable and was estimated from the contralateral side. In soleus most denervations ranged from 83 to 99%; in FDL, from 37 to 81%. 4. In both soleus and FDL there was no evidence that the motor units had sprouted to any less extent than found previously. Within some soleus muscles the largest motor units were developing substantially more force than was expected. However, determination of mean fiber cross-sectional area from muscles frozen, sectioned, and prepared for histochemical analysis showed that this was attributable to increased mean cross-sectional area of the type I fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

Enlarged motor units resulting from partial denervation of cat hindlimb muscles

1988 ◽  
Vol 59 (5) ◽  
pp. 1377-1394 ◽  
Author(s):  
A. R. Luff ◽  
D. D. Hatcher ◽  
K. Torkko
Keyword(s):  
Motor Unit ◽  
Soleus Muscle ◽  
Motor Units ◽  
Motor Axons ◽  
Unit Force ◽  
Single Motor Units ◽  
Partial Denervation ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Polyneuronal Innervation

1. It was the aim of this study to determine the extent to which a mammalian motoneuron can sprout in a partially denervated muscle, which motor unit types are involved in sprouting, and whether polyneuronal innervation exists between sprouted units. 2. The fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus were partially denervated by unilateral section of the L7 ventral root in 12-wk-old kittens. After approximately 100 days single motor units were isolated, and their isometric contractile characteristics were determined. FDL units were also tested for their resistance to fatigue and categorized as fast-twitch, fatiguing fibers (FF), fast-twitch, fatigue-resistant fibers (FR), and slow-twitch, fatigue-resistant fibers (S). The presence of polyneuronal innervation was investigated between pairs of like and unlike units. 3. The extent of the original denervation was variable and was estimated from the distribution of motor axons innervating the muscle via the L7 and S1 (soleus) or L6 and L7 (FDL) ventral roots on the contralateral side. In soleus, denervations ranged from 75 to 98%; in FDL, 60 to 97% (denervations less than 60% were not investigated). In general, motor-unit force increased in proportion to the extent of the denervation. 4. Within soleus, unit force increased to over 2 N, which was about 16 times greater than the average for a normal muscle (133 mN). However, most units increased in force to between five and 12 times normal. 5. Within FDL, the force development of type S units was unaffected by partial denervation. Type FF units increased by up to 11 times (4.3 N) compared with normal FF units (395 mN) with most increasing between two and four times. FR units exhibited the greatest relative increase in force [up to 19 times (4.3 N) compared with normal (225 mN)]. Most units were two to seven times the normal. 6. A few FDL units were glycogen depleted, the muscles frozen, and cross sections prepared for histochemical analysis. This indicated that the largest units contained approximately 5,000 fibers, and there was little fiber hypertrophy. In the extensively denervated soleus muscle, large numbers of small, presumably denervated fibers were observed. The innervation ratio of several large units was determined indirectly using mean fiber area. This gave estimates of 3,000-4,000 fibers for the largest units. Again, fiber hypertrophy contributed little to the increase in unit force. It was concluded that the increased force of units in both muscles was largely attributable to terminal and axonal sprouting of the intact motor axons. 7. No evidence for polyneuronal innervation was found in either FDL or soleus muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

Studies of the halothane-cooling contractures of skeletal muscle

1987 ◽  
Vol 65 (4) ◽  
pp. 697-703 ◽  
Author(s):  
Roberto T. Sudo ◽  
Gisele Zapata ◽  
Guilherme Suarez-Kurtz
Keyword(s):  
Skeletal Muscle ◽  
Synergistic Effects ◽  
Rabbit Muscle ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Dose Dependent ◽  
Muscle Biopsies ◽  
Ca Homeostasis ◽  
Potential Use

The characteristics of transient contractures elicited by rapid cooling of frog or mouse muscles perfused in vitro with solutions equilibrated with 0.5–2.0% halothane are reviewed. The data indicate that these halothane-cooling contractures are dose dependent and reproducible, and their amplitude is larger in muscles containing predominantly slow-twitch type fibers, such as the mouse soleus, than in muscles in which fast-twitch fibers predominate, such as the mouse extensor digitorum longus. The halothane-cooling contractures are potentiated in muscles exposed to succinylcholine. The effects of Ca2+-free solutions, of the local anesthetics procaine, procainamide, and lidocaine, and of the muscle relaxant dantrolene on the halothane-cooling contractures are consistent with the proposal that the halothane-cooling contractures result from synergistic effects of halothane and low temperature on Ca sequestration by the sarcoplasmic reticulum. Preliminary results from skinned rabbit muscle fibers support this proposal. The halothane concentrations required for the halothane-cooling contractures of isolated frog or mouse muscles are comparable with those observed in serum of patients during general anesthesia. Accordingly, fascicles dissected from muscle biopsies of patients under halothane anesthesia for programmed surgery develop large contractures when rapidly cooled. The amplitude of these halothane-cooling contractures declined with the time of perfusion of the muscle fascicles in vitro with halothane-free physiological solutions. It is suggested that the halothane-cooling contractures could be used as a simple experimental model for the investigation of the effects of halothane on Ca homeostasis and contractility in skeletal muscle and for study of drugs of potential use in the management of the contractures associated with the halothane-induced malignant hyperthermia syndrome. It is shown that salicylates, but not indomethacin or mefenamic acid, inhibit the halothane-cooling contractures.

scholarly journals The Functional Role of Calcineurin in Hypertrophy, Regeneration, and Disorders of Skeletal Muscle

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Kunihiro Sakuma ◽  
Akihiko Yamaguchi
Keyword(s):  
Skeletal Muscle ◽  
Functional Role ◽  
Muscular Hypertrophy ◽  
Growth And Remodeling ◽  
Muscular Disorders ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Calcineurin Activity ◽  
Muscle Remodeling

Skeletal muscle uses calcium as a second messenger to respond and adapt to environmental stimuli. Elevations in intracellular calcium levels activate calcineurin, a serine/threonine phosphatase, resulting in the expression of a set of genes involved in the maintenance, growth, and remodeling of skeletal muscle. In this review, we discuss the effects of calcineurin activity on hypertrophy, regeneration, and disorders of skeletal muscle. Calcineurin is a potent regulator of muscle remodeling, enhancing the differentiation through upregulation of myogenin or MEF2A and downregulation of the Id1 family and myostatin. Foxo may also be a downstream candidate for a calcineurin signaling molecule during muscle regeneration. The strategy of controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as DMD, UCMD, and LGMD. Activation of calcineurin produces muscular hypertrophy of the slow-twitch soleus muscle but not fast-twitch muscles.

Guinea pig soleus and gastrocnemius electromyograms at varying speeds, grades, and loads

1982 ◽  
Vol 52 (2) ◽  
pp. 451-457 ◽  
Author(s):  
K. R. Gardiner ◽  
P. F. Gardiner ◽  
V. R. Edgerton
Keyword(s):  
Guinea Pig ◽  
Work Load ◽  
Burst Duration ◽  
Lateral Gastrocnemius ◽  
Biochemical Alterations ◽  
Hindlimb Muscles ◽  
Slow Twitch ◽  
Fast Twitch ◽  
Grade Increase ◽  
Emg Electrodes

The purpose of the study was to describe changes that occur in the usage of fast-twitch and slow-twitch guinea pig hindlimb muscles, as estimated using chronically implanted electromyogram (EMG) electrodes, during voluntary locomotion under various conditions. Guinea pigs, in which fine wire electrodes were implanted in soleus (SOL) and lateral gastrocnemius (LG) muscles, were exercised at various speeds (13.4, 26.8, 40.2 m/min), grades (0–30%) and in some conditions loads (50–150 g) on a motor-driven treadmill. Bipolar EMG signals were rectified-averaged (RA-EMG) and analyzed for burst duration, amplitude, and the integral of each burst (IEMG). For each condition and muscle, total IEMG/min (IEMG/step x steps/min) was calculated and expressed as a percent of the maximum IEMG recorded. With increasing speed at 0% grade, the ratio of LG to SOL IEMG, each expressed as percent of maximum, remained constant at about 0.82. An increased stepping rate of 150 (at 13.4 m/min) to 225 (at 40.2 m/min) steps/min was accompanied by a 37% decrease in burst duration in LG and SOL. When the treadmill belt speed was increased from 13.4 to 4.02 m/min at 30% grade, the LG/SOL ratio increased from 0.83 to 1.03, whereas burst duration decreased by 49% (SOL) and 51% (LG). Soleus IEMG did not change significantly with increases in speed or grade; LG IEMG increased significantly with speed at 10% grade and with grade increase at the highest speed (40.2 m/min). These data provide some insight into how modifications of work load on a treadmill affect overall muscle activity and may assist in the interpretation of training-induced muscle biochemical alterations previously noted by other investigators.

Glutamine synthetase induction by glucocorticoids is preserved in skeletal muscle of aged rats

1996 ◽  
Vol 271 (6) ◽  
pp. E1061-E1066 ◽  
Author(s):  
D. Meynial-Denis ◽  
M. Mignon ◽  
A. Miri ◽  
J. Imbert ◽  
E. Aurousseau ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glutamine Synthetase ◽  
Skeletal Muscles ◽  
Female Rats ◽  
Mrna Levels ◽  
Aged Rats ◽  
Adult Rats ◽  
Adult Age ◽  
Slow Twitch ◽  
Fast Twitch

Glutamine synthetase (GS) is a glucocorticoid-inducible enzyme that has a key role for glutamine synthesis in muscle. We hypothesized that the glucocorticoid induction of GS could be altered in aged rats, because alterations in the responsiveness of some genes to glucocorticoids were reported in aging. We compared the glucocorticoid-induced GS in fast-twitch and slow-twitch skeletal muscles (tibialis anterior and soleus, respectively) and heart from adult (age 6-8 mo) and aged (age 22 mo) female rats. All animals received dexamethasone (Dex) in their drinking water (0.77 +/- 0.10 and 0.80 +/- 0.08 mg/day per adult and aged rat, respectively) for 5 days. Dex caused an increase in both GS activity and GS mRNA in fast-twitch and slow-twitch skeletal muscles from adult and aged rats. In contrast, Dex increased GS activity in heart of adult rats, without any concomitant change in GS mRNA levels. Furthermore, Dex did not affect GS activity in aged heart. Thus the responsiveness of GS to an excess of glucocorticoids is preserved in skeletal muscle but not in heart from aged animals.

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