Force regulation and electrical properties of motor units in overloaded muscle

Kryściak, Katarzyna; Celichowski, Jan; Drzymała‐Celichowska, Hanna; Gardiner, Phillip F.; Krutki, Piotr

doi:10.1002/mus.24690

Cited by 5 publications

(16 citation statements)

References 43 publications

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“…Considering the progressive differential susceptibility of fast MU in ALS (Frey et al, 2000;Atkin et al, 2005;Pun et al, 2006;Hegedus et al, 2007Hegedus et al, , 2008, we postulated that previous inconsistencies seen in synaptic transmission at the NMJ in various ALS models may be explained by the differential effect of the mutation on the different MU types. In addition, we hypothesized that synaptic alterations presented by the various NMJ types (S-FR-FF) might be transient and evolve differently as disease progresses.…”

Section: Resultsmentioning

confidence: 87%

“…However, since several morphological alterations have been reported in the SOD1 G93A mouse before symptom onset, especially in FF MUs (Frey et al, 2000;Pun et al, 2006;Valdez et al, 2012), we expected substantial denervation and postsynaptic changes in the fast-twitch EDL that could impair synaptic transmission during the preonset stage. The three components of the NMJ were then labeled at P380 on EDL and SOL whole-mounted muscle preparations, and each NMJ was analyzed according to the seven criteria previously described (Fig.…”

Section: At Preonset Stage: Nmj Morphology Is Altered In the Edl And mentioning

confidence: 76%

“…The following steps of the immunostaining were performed at room temperature. After a rinsing period (three times with PBS), muscles were incubated in a PBS- Immunolabeling on cross sections of the EDL was performed as previously described (Gouspillou et al, 2014). Briefly, EDL muscles were mounted in cold optimal cutting temperature compound (OCT; Tissue-Tek) and frozen in isopentane cooled to Ϫ80°C in liquid nitrogen.…”

Section: Immunohistochemistry and Fiber Type Identificationmentioning

confidence: 99%

“…Denervation and loss of synaptic proteins (e.g., SV2) were observed in SOD1 G93A mice, while early stalling of synaptic vesicles in the nerve terminal has been preferentially observed in fasttwitch fibers (Pun et al, 2006). These changes occur before the onset of symptoms and the loss of ventral root axons in the spinal cord (Frey et al, 2000;Fischer et al, 2004;Narai et al, 2009). This loss affects primarily fast-fatigable (FF) motor units (MUs), as they show the greatest vulnerability, followed by fast fatigue-resistant (FR) and slow (S) MUs, the latter being the most resistant that persist until end-stage (Frey et al, 2000;Pun et al, 2006;Hegedus et al, 2007Hegedus et al, , 2008.…”

Section: Introductionmentioning

confidence: 99%

“…These changes occur before the onset of symptoms and the loss of ventral root axons in the spinal cord (Frey et al, 2000;Fischer et al, 2004;Narai et al, 2009). This loss affects primarily fast-fatigable (FF) motor units (MUs), as they show the greatest vulnerability, followed by fast fatigue-resistant (FR) and slow (S) MUs, the latter being the most resistant that persist until end-stage (Frey et al, 2000;Pun et al, 2006;Hegedus et al, 2007Hegedus et al, , 2008. Large MUs in fast-twitch muscles are then partially replaced by compensatory reinnervation by axons from small (S and FR) MUs (Schaefer et al, 2005;Hegedus et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter

2017

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Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotrophic lateral sclerosis (ALS). ALS is characterized by a motor unit (MU)-dependent vulnerability where MNs with fast-fatigable (FF) characteristics are lost first, followed by fast fatigue-resistant (FR) and slow (S) MNs. However, changes in NMJ properties as a function of MU types remain debated. We hypothesized that NMJ synaptic functions would be altered precociously in an MU-specific manner, before structural alterations of the NMJ. Synaptic transmission and morphological changes of NMJs have been explored in two nerve-muscle preparations of male mice and their wild-type (WT) littermates: the soleus (S and FR MU); and the extensor digitorum longus (FF MU). S, FR, and FF NMJs of WT mice showed distinct synaptic properties from which we build an MU synaptic profile (MUSP) that reports MU-dependent NMJ synaptic properties. At postnatal day 180 (P180), FF and S NMJs of SOD1 already showed, respectively, lower and higher quantal content compared with WT mice, before signs of MN death and before NMJ morphological alterations. Changes persisted in both muscles until preonset (P380), while denervation was frequent in the mutant mouse. MN death was evident at this stage. Additional changes occurred at clinical disease onset (P450) for S and FR MU. As a whole, our results reveal a reversed MUSP in SOD1 mutants and highlight MU-specific synaptic changes occurring in a precise temporal sequence. Importantly, changes in synaptic properties appear to be good predictors of vulnerability to neurodegeneration. The inadequate excitability of motor neurons and their output, the neuromuscular junctions (NMJs), has been considered a key factor in the detrimental outcome of the motor function in amyotrophic lateral sclerosis. However, a conundrum persists at the NMJ whereby persistent but incoherent opposite neurotransmission changes have been reported to take place. This article untangles this conundrum by systematically analyzing the changes in synaptic properties over the course of the disease progression as a function of the motor unit type. This temporal analysis reveals that early synaptic alterations evolve with disease progression but precede NMJ neurodegeneration. These data provide a novel framework of analysis and comparison of synaptic transmission alterations in neurodegenerative disorders.

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Section: Resultsmentioning

confidence: 87%

Section: At Preonset Stage: Nmj Morphology Is Altered In the Edl And mentioning

confidence: 76%

Section: Immunohistochemistry and Fiber Type Identificationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter

2017

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Motor Units and Muscle Receptors

Celichowski¹,

Krutki²

2019

Muscle and Exercise Physiology

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A model of the rat medial gastrocnemius muscle based on inputs to motoneurons and on an algorithm for prediction of the motor unit force

Raikova

Celichowski²,

Angelova

et al. 2018

Journal of Neurophysiology

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The muscle force is the sum of forces of multiple motor units (MUs), which have different contractile properties. During movements, MUs develop unfused tetani, which result from summation of twitch-shape responses to individual stimuli, which are variable in amplitude and duration. The aim of the study was to develop a realistic muscle model that would integrate previously developed models of MU contractions and an algorithm for the prediction of tetanic forces. The proposed model of rat medial gastrocnemius muscle is based on physiological data: excitability and firing frequencies of motoneurons, contractile properties, and the number and proportion of MUs in the muscle. The MU twitches were modeled by a six-parameter analytical function. The excitability of motoneurons was modeled according to a distribution of their rheobase currents measured experimentally. Processes of muscle force regulation were modeled according to a common drive hypothesis. The excitation signal to motoneurons was modeled by two form types: triangular and trapezoid. The discharge frequencies of MUs, calculated individually for each MU, corresponded to those recorded for rhythmic firing of motoneurons. The force of the muscle was calculated as the sum of all recruited MUs. Participation of the three types of MUs in the developed muscle force was presented at different levels of the excitation signal to motoneurons. The model appears highly realistic and open for input data from various skeletal muscles with different compositions of MU types. The results were compared with three other models with different distribution of the input parameters. NEW & NOTEWORTHY The proposed mathematical model of rat medial gastrocnemius muscle is highly realistic because it is based strictly on experimentally determined motor unit contractile parameters and motoneuron properties. It contains the actual number and proportion of motor units and takes into consideration their different contributions to the whole muscle force, depending on the level of the excitation signal. The model is open for input data from other muscles, and additional physiological parameters can also be included.

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Force regulation and electrical properties of motor units in overloaded muscle

Abstract: Compensatory muscle overload leads to substantial modifications in MU force development mechanisms, which are MU-type-specific and influence whole muscle force regulation.

Cited by 5 publications

References 43 publications

Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter

Opposite Synaptic Alterations at the Neuromuscular Junction in an ALS Mouse Model: When Motor Units Matter

Motor Units and Muscle Receptors

A model of the rat medial gastrocnemius muscle based on inputs to motoneurons and on an algorithm for prediction of the motor unit force

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