scholarly journals Chronic hypoxia modulates diaphragm function in the developing rat

2001 ◽  
Vol 90 (6) ◽  
pp. 2325-2329 ◽  
Author(s):  
L. J. Kass ◽  
A. R. Bazzy

We studied the effect of chronic hypoxia on contractile properties and neuromuscular transmission in the developing rat diaphragm. We hypothesized that chronic hypoxia delays maturation of neuromuscular transmission. Phrenic nerve hemidiaphragm preparations were harvested from 3- to 26-day-old rats and littermates raised in 9.5% oxygen. Specific force, contraction time, and one-half relaxation time were measured. Each diaphragm was stimulated directly or via its nerve with 1-s trains at 10–100 Hz. Contraction time and one-half relaxation time decreased with advancing age in both groups, with a greater rate of decrease in hypoxic diaphragms. Specific force was lower for hypoxic diaphragms compared with controls. Diaphragms from the 3- to 10-day-old control and hypoxic groups generated less force in response to stimulation at frequencies >40 Hz but did so to a greater degree with nerve stimulation. Nerve stimulation of diaphragms from 11- to 18-day-old hypoxic rats showed a greater decrease in force with increasing frequency compared with age-matched controls. Diaphragms from 19- to 26-day-old rats showed no difference between the hypoxic and control groups. We conclude that chronic hypoxia leads to diaphragms that generate lower specific force as well as to a delayed maturation of mechanisms involved in neuromuscular transmission.

2019 ◽  
Vol 122 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Matthew J. Fogarty ◽  
Maria A. Gonzalez Porras ◽  
Carlos B. Mantilla ◽  
Gary C. Sieck

In aging Fischer 344 rats, phrenic motor neuron loss, neuromuscular junction abnormalities, and diaphragm muscle (DIAm) sarcopenia are present by 24 mo of age, with larger fast-twitch fatigue-intermediate (type FInt) and fast-twitch fatigable (type FF) motor units particularly vulnerable. We hypothesize that in old rats, DIAm neuromuscular transmission deficits are specific to type FInt and/or FF units. In phrenic nerve/DIAm preparations from rats at 6 and 24 mo of age, the phrenic nerve was supramaximally stimulated at 10, 40, or 75 Hz. Every 15 s, the DIAm was directly stimulated, and the difference in forces evoked by nerve and muscle stimulation was used to estimate neuromuscular transmission failure. Neuromuscular transmission failure in the DIAm was observed at each stimulation frequency. In the initial stimulus trains, the forces evoked by phrenic nerve stimulation at 40 and 75 Hz were significantly less than those evoked by direct muscle stimulation, and this difference was markedly greater in 24-mo-old rats. During repetitive nerve stimulation, neuromuscular transmission failure at 40 and 75 Hz worsened to a greater extent in 24-mo-old rats compared with younger animals. Because type IIx and/or IIb DIAm fibers (type FInt and/or FF motor units) display greater susceptibility to neuromuscular transmission failure at higher frequencies of stimulation, these data suggest that the age-related loss of larger phrenic motor neurons impacts nerve conduction to muscle at higher frequencies and may contribute to DIAm sarcopenia in old rats. NEW & NOTEWORTHY Diaphragm muscle (DIAm) sarcopenia, phrenic motor neuron loss, and perturbations of neuromuscular junctions (NMJs) are well described in aged rodents and selectively affect FInt and FF motor units. Less attention has been paid to the motor unit-specific aspects of nerve-muscle conduction. In old rats, increased neuromuscular transmission failure occurred at stimulation frequencies where FInt and FF motor units exhibit conduction failures, along with decreased apposition of pre- and postsynaptic domains of DIAm NMJs of these units.


1999 ◽  
Vol 86 (3) ◽  
pp. 840-844 ◽  
Author(s):  
M. van Leemputte ◽  
K. Vandenberghe ◽  
P. Hespel

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 × 5 g/day; n = 8) or placebo ( n = 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by ∼20% ( P < 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT ( r = 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.


1976 ◽  
Vol 144 (3) ◽  
pp. 739-753 ◽  
Author(s):  
J M Lindstrom ◽  
A G Engel ◽  
M E Seybold ◽  
V A Lennon ◽  
E H Lambert

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.


1987 ◽  
Vol 62 (6) ◽  
pp. 2314-2319 ◽  
Author(s):  
J. S. Arnold ◽  
A. J. Thomas ◽  
S. G. Kelsen

The present study examined the intrinsic contractile properties and endurance of the transverse abdominis and external oblique abdominal expiratory muscles in adult hamsters and compared their performance with the diaphragm. Experiments were performed in vitro on isolated bundles of muscle stimulated electrically. In control animals peak twitch tension was similar in the two muscles. In contrast, the twitch contraction time and one-half relaxation time of the transverse abdominis were significantly greater than that of the external oblique. The isometric tension generated over a range of stimulus frequencies (i.e., the force-frequency relationship) was a greater percent of the maximum value in response to subtetanizing frequencies (10–40 Hz) in the transverse abdominis than in the external oblique. For both abdominal muscles, however, the tension generated over this range of stimulus frequencies was less than that of the diaphragm. The endurance of the transverse abdominis during repeated contractions was significantly greater than that of the external oblique but similar to the diaphragm. The effect of chronic hyperinflation produced by elastase-induced emphysema on the contractile function of the two muscles was assessed in a second group of adult hamsters. In emphysematous animals peak twitch tension, contraction time, and one-half relaxation time of the twitch and force-frequency curves of muscles from emphysematous animals were similar to values obtained in control animals for both the external oblique and transverse abdominis. However, the endurance of both the transverse abdominis and external oblique muscles was greater in emphysematous than control animals.(ABSTRACT TRUNCATED AT 250 WORDS)


1991 ◽  
Vol 66 (5) ◽  
pp. 1483-1492 ◽  
Author(s):  
T. C. Cope ◽  
C. B. Webb ◽  
A. K. Yee ◽  
B. R. Botterman

1. The endurance of slow-twitch motor units from the soleus (SOL) and medial gastrocnemius (MG) muscles of the cat were tested by determining the length of time (endurance time, Et) that a unit could maintain its tension output at 85% of maximum. Motor-unit tension was clamped at the target level by altering the stimulation rate of a unit's motor axon through computer feedback control. Tested in this way, units of both muscles displayed a wide range of Ets, approximately 40- to 50-fold. 2. Electromyographic (EMG) waveforms of motor units subjected to force-clamp contractions were analyzed to access whether any activity-dependent changes in their waveform shape might predict Et. Three measurements of waveform shape were determined: baseline-to-baseline duration, peak-to-peak amplitude, and area. Typically, amplitude decreased and duration increased as a contraction proceeded, whereas area remained fairly constant. Because changes in each measure were very similar for units of widely different Ets, it was concluded that neuromuscular junction failure and changes in the excitability of the sarcolemma (excluding the t-tubule system) play a minor role in determining Et. 3. Et was highly correlated with the mean stimulation rate (Et/number of stimuli) used during the force-clamp contractions. Mean rate was seen to progressively decrease with increasing Et. This correlation could not be explained by measures of isometric contractile speed or relaxation (e.g., twitch contraction time or half-relaxation time) measured before the force-clamp contractions. Both contraction time and half-relaxation time were found to be unrelated to both Et and the rate used to stimulate the unit during the force-clamp contraction. 4. Among type S units of SOL and MG, maximum tetanic tension and Et were not related. A significant relation (r = -0.49) was found between axonal conduction velocity and Et for SOL units (n = 38). In addition, a significant correlation (r = 0.47) was found between conduction velocity and tetanic tension for SOL units. Perhaps because of the small sample of type S units from MG (n = 10), conduction velocity was found not be related to either Et or tetanic tension. 5. Others have shown that a motor unit's maximum tetanic tension and axonal conduction velocity are correlated with its order of recruitment among motoneurons innervating a muscle. Recent work has further shown that among type F units the order in which a motoneuron is recruited is highly correlated with the fatigue resistance of its muscle unit.(ABSTRACT TRUNCATED AT 400 WORDS)


2016 ◽  
pp. 328-346
Author(s):  
Kathleen D. Kennelly

Repetitive stimulation is a technique that evaluates the function of the neuromuscular junction. It is important not only in the detection, clarification, and follow-up of neuromuscular junction diseases, but also in excluding these disorders in patients with symptoms of fatigue, vague weakness, diplopia, ptosis, and malaise, or with objective weakness of uncertain origin. The technique requires knowledge of the physiology and pathophysiology of neuromuscular transmission and the basic techniques of nerve conduction studies. This chapter includes a brief review of the anatomy and physiology of the neuromuscular junction as it applies to repetitive stimulation, a detailed discussion of the technique, the pitfalls that can occur if not carried out correctly, criteria used to classify the results as normal or abnormal, the patterns of abnormalities that can be seen, and the clinical correlation of those abnormalities with the various different disorders of neuromuscular transmission.


1958 ◽  
Vol 192 (3) ◽  
pp. 464-470 ◽  
Author(s):  
Choh-Luh Li ◽  
Peter Gouras

Recording with intracellular electrodes from endplate regions of frogs sartorius muscle showed that at –1°C miniature endplate potentials still occurred and that the resting membrane potentials differed very little from those recorded at room temperatures. The miniature potentials, however, were decreased in frequency and increased in amplitude by cooling; and at about 5°C, the amplitude began to fall while the frequency continued to be low. It was also at about 5°C that the muscle responses to nerve stimulation frequently consisted of endplate potentials only. Upon rewarming spike potentials again appeared. These observations suggest that there is a critical temperature for neuromuscular transmission, below which impediment of impulse transmission began; and in the frog it is 5°C. The experiments also demonstrated that during the process of cooling a blockage of impulses at one neuromuscular junction and transmission across the other in a single muscle fiber could occur.


2001 ◽  
Vol 281 (1) ◽  
pp. H132-H138 ◽  
Author(s):  
R. M. Mohan ◽  
S. Golding ◽  
D. J. Paterson

Nitric oxide (NO) decreases norepinephrine (NE) release and the heart rate (HR) response to sympathetic nerve stimulation (SNS). We tested the hypothesis that the enhanced HR response to sympathetic activation following chronic intermittent hypoxia (IH) results from a peripheral modulation of pacemaking by NO. Isolated guinea pig double atrial/right stellate ganglion preparations were studied from animals that had been exposed to IH ( n = 20) and control animals ( n = 22). The HR response to SNS was significantly enhanced in the IH group compared with the controls. However, the increase in HR with cumulative doses (0.1–10 μM) of bath-applied NE was similar in both groups. Western blot analysis showed less neuronal NO synthase in the right atria from the IH group. In IH animals, the NO synthase inhibitor, N ω-nitro-l-arginine (l-NNA; 100 μM) did not alter the increased HR response to SNS, whereas in control animals l-NNA significantly increased the HR response to SNS; an effect that was reversed with excess l-arginine. In conclusion, the enhanced HR response to SNS after IH may be related to a decreased inhibitory action of NO on presynaptic NE release.


1963 ◽  
Vol 204 (3) ◽  
pp. 433-438 ◽  
Author(s):  
Zia J. Penefsky ◽  
Brian F. Hoffman

A comparative study was made of effects of stretch on cat papillary muscle and auricle strips, hamster ventricular wall, ground squirrel ventricular strip, chicken auricle and ventricle, terrapin auricle and ventricle strips, and carp ventricle. In all species mild stretch increased contractile tension, excessive stretch decreased it, and velocity of conduction was constant with mild stretch but decreased with excessive stretch. In homeotherms under mild stretch, contraction time was unchanged and increased contractile tension was accompanied by increase in velocity of contraction. Under excessive stretch contraction time increased despite decreasing contractile tension. In poikilotherms contraction time and contractile tension were increased by mild stretch. Contraction time decreased with excessive stretch. Stretch increased relaxation time in all species. The evidence suggests that decrease in contractile tension with stretch is related, at least in the initial phases, to a change in excitability and conduction. In all species mild stretch was without effect on transmembrane action potentials, whereas at excessive stretch resting potentials and overshoot declined and rise time of the action potential was greatly increased. At excessive stretch surface-recorded potentials exhibited polyphasic deflections. All observed responses to stretch were reversible. Immediately after stretch the fibers were slightly elongated but developed a higher maximal contractile tension, and contraction time also was slightly increased.


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