Calcium Movements Research Articles

Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

Identification of uterine ion transporters for mineralisation precursors of the avian eggshell.

BackgroundIn Gallus gallus, eggshell formation takes place daily in the hen uterus and requires large amounts of the ionic precursors for calcium carbonate (CaCO3). Both elements (Ca2+, HCO3-) are supplied by the blood via trans-epithelial transport. Our aims were to identify genes coding for ion transporters that are upregulated in the uterine portion of the oviduct during eggshell calcification, compared to other tissues and other physiological states, and incorporate these proteins into a general model for mineral transfer across the tubular gland cells during eggshell formation.ResultsA total of 37 candidate ion transport genes were selected from our database of overexpressed uterine genes associated with eggshell calcification, and by analogy with mammalian transporters. Their uterine expression was compared by qRTPCR in the presence and absence of eggshell formation, and with relative expression levels in magnum (low Ca2+/HCO3- movement) and duodenum (high rates of Ca2+/HCO3- trans-epithelial transfer). We identified overexpression of eleven genes related to calcium movement: the TRPV6 Ca2+ channel (basolateral uptake of Ca2+), 28 kDa calbindin (intracellular Ca2+ buffering), the endoplasmic reticulum type 2 and 3 Ca2+ pumps (ER uptake), and the inositol trisphosphate receptors type 1, 2 and 3 (ER release). Ca2+ movement across the apical membrane likely involves membrane Ca2+ pumps and Ca2+/Na+ exchangers. Our data suggests that Na+ transport involved the SCNN1 channel and the Na+/Ca2+ exchangers SLC8A1, 3 for cell uptake, the Na+/K+ ATPase for cell output. K+ uptake resulted from the Na+/K+ ATPase, and its output from the K+ channels (KCNJ2, 15, 16 and KCNMA1).We propose that the HCO3- is mainly produced from CO2 by the carbonic anhydrase 2 (CA2) and that HCO3- is secreted through the HCO3-/Cl- exchanger SLC26A9. HCO3- synthesis and precipitation with Ca2+ produce two H+. Protons are absorbed via the membrane’s Ca2+ pumps ATP2B1, 2 in the apical membrane and the vacuolar (H+)-atpases at the basolateral level. Our model incorporate Cl- ions which are absorbed by the HCO3-/Cl- exchanger SLC26A9 and by Cl- channels (CLCN2, CFTR) and might be extruded by Cl-/H+ exchanger (CLCN5), but also by Na+ K+ 2 Cl- and K+ Cl- cotransporters.ConclusionsOur Gallus gallus uterine model proposes a large list of ion transfer proteins supplying Ca2+ and HCO3- and maintaining cellular ionic homeostasis. This avian model should contribute towards understanding the mechanisms and regulation for ionic precursors of CaCO3, and provide insight in other species where epithelia transport large amount of calcium or bicarbonate.

Ion distribution measured by electron probe X-ray microanalysis in apoplastic and symplastic pathways in root cells in sunflower plants grown in saline medium

Little is known about how salinity affects ions distribution in root apoplast and symplast. Using x-ray microanalysis, ions distribution and the relative contribution of apoplastic and symplastic pathways for delivery of ions to root xylem were studied in sunflower plants exposed to moderate salinity (EC=6). Cortical cells provided a considerably extended Na(+) and Cl(-) storage facility. Their contents are greater in cytoplasm (root symplast) as compared to those in intercellular spaces (root apoplast). Hence, in this level of salinity, salt damage in sunflower is not dehydration due to extracellular accumulation of sodium and chloride ions, as suggested in the Oertli hypothesis. On the other hand, reduction in calcium content due to salinity in intercellular space is less than reduction in the cytoplasm of cortical cells. It seems that sodium inhibits the radial movement of calcium in symplastic pathway more than in the apoplastic pathway. The cell wall seems to have an important role in providing calcium for the apoplastic pathway. Redistribution of calcium from the cell wall to intercellular space is because of its tendency towards xylem through the apoplastic pathway. This might be a strategy to enhance loading of calcium to xylem elements and to reduce calcium deficiency in young leaves under salinity. This phenomenon may be able to increase salt tolerance in sunflower plants. Supplemental calcium has been found to be effective in reducing radial transport of Na(+) across the root cells and their loading into the xylem, but not sodium absorption. Supplemental calcium enhanced Ca(2+) uptake and influx into roots and transport to stele.

Animal welfare in the newborn piglet: a review

The objective of this review is to integrate clinical findings and laboratory analyses in such a way to improve the welfare of newborn piglets and achieve better prognoses of neonatal viability. Deaths during the intrapartum period account for a significant proportion of pre-weaning mortality in farms worldwide. Piglets which die during parturition generally have normal size and typically lack gross lesions at post-mortem examination. However, circulatory abnormalities in the umbilical cord help in assessing piglet viability. Cord lesions can be classified as normal (adhered), oedematous, congested or haemorrhagic and should always be evaluated in perinatal deaths. The likelihood of neonatal survival decreases rapidly as the severity of umbilical cord lesions increase. The physiometabolic blood profile which includes acid-base balance, degree of dehydration, mineral balance, metabolic expenditure and gas exchange are also useful clinical elements for properly assessing neonatal viability. Neonatal survival is notably reduced when the blood pH falls below 7.0, lactate rises above 90 mg/dl, bicarbonate drops below 10 mmol/l, or the pCO<sub>2</sub> increases above 110 mm/Hg. Blood calcium is also an excellent indicator of neonatal stress when used in combination with the other parameters mentioned above. Trembling due to an imbalance in the movement of calcium in muscle is also a factor involved in neonatal mortality. Neurological function in the newborn piglet could also be evaluated by adapting the Apgar score widely used in human perinatology. Neonates with scores lower than 6 in a 10 point scale have generally lower survival rates. The two most important indicators for this vitality score are breathing latency and bradycardia. If the neonate has apnoea for more than 5 min and the cardiac frequency does not increase to more than 110 beats per minute the prognosis for survival is rather poor.  

Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction

Uncoupling proteins (UCPs) belong to a large family of mitochondrial solute carriers 25 (SLC25s) localized at the inner mitochondrial membrane. UCPs transport protons directly from the intermembrane space to the matrix. Of five structural homologues (UCP1 to 5), UCP4 and 5 are principally expressed in the central nervous system (CNS). Neurons derived their energy in the form of ATP that is generated through oxidative phosphorylation carried out by five multiprotein complexes (Complexes I–V) embedded in the inner mitochondrial membrane. In oxidative phosphorylation, the flow of electrons generated by the oxidation of substrates through the electron transport chain to molecular oxygen at Complex IV leads to the transport of protons from the matrix to the intermembrane space by Complex I, III, and IV. This movement of protons to the intermembrane space generates a proton gradient (mitochondrial membrane potential; MMP) across the inner membrane. Complex V (ATP synthase) uses this MMP to drive the conversion of ADP to ATP. Some electrons escape to oxygen-forming harmful reactive oxygen species (ROS). Proton leakage back to the matrix which bypasses Complex V resulting in a major reduction in ROS formation while having a minimal effect on MMP and hence, ATP synthesis; a process termed “mild uncoupling.” UCPs act to promote this proton leakage as means to prevent excessive build up of MMP and ROS formation. In this review, we discuss the structure and function of mitochondrial UCPs 4 and 5 and factors influencing their expression. Hypotheses concerning the evolution of the two proteins are examined. The protective mechanisms of the two proteins against neurotoxins and their possible role in regulating intracellular calcium movement, particularly with regard to the pathogenesis of Parkinson's disease are discussed.

Intracellular calcium movements during excitation–contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers

In skeletal muscle fibers, action potentials elicit contractions by releasing calcium ions (Ca2+) from the sarcoplasmic reticulum. Experiments on individual mouse muscle fibers micro-injected with a rapidly responding fluorescent Ca2+ indicator dye reveal that the amount of Ca2+ released is three- to fourfold larger in fast-twitch fibers than in slow-twitch fibers, and the proportion of the released Ca2+ that binds to troponin to activate contraction is substantially smaller.

Do calcium fluxes within cortical bone affect osteocyte mechanosensitivity?

Bone reacts to local mechanical environment by adapting its structure. Bone is also a key source of calcium for the body homeostasis. Osteocytes, cells located within the bone tissue, are thought to play a major role in sensing mechanical signals and regulating bone remodeling. Interestingly, osteocytes were also shown to directly participate in the calcium homeostasis by regulating dissolution and deposition of calcium in the perilacuno-pericanalicular space. However, it is not known if osteocyte's roles in mechanoregulation and calcium homeostasis have any significant crosstalk. Previously, a multi-scale mathematical model of the interstitial fluid flow through the canaliculus was developed, which took into account physicochemical phenomena including hydraulic effects, formation of electrical double layer, osmosis and electro-osmosis. We extended this model to include the directional movement of calcium from and into the bone tissue, and assessed the shear stress at the osteocyte membrane. We have found that in the bulk of the canalicular space the fluid flow due to chemical gradient generated by deposition or dissolution of calcium is negligible compared to the fluid flow due to hydraulic pressure. However, at the osteocyte proximity, the presence of calcium gradient generated sufficient fluid flow to induce significant changes in the shear stress on the osteocyte membrane. Calcium deposition and dissolution on the canalicular wall resulted in increased or decreased shear stress on the osteocyte membrane respectively. Thus, our data demonstrate that strong calcium fluxes due to whole body calcium homeostasis may affect mechanical forces experienced by osteocytes.

Localization, Distribution, and Function of the Calcium‐Sensing Receptor in Sperm

The intracellular movement of calcium, through calcium channels, plays a major role on sperm cell function. The calcium-sensing receptor (CaSR), a molecular mechanism by which many cells detect changes in extracellular calcium concentration, has not been described in spermatozoa. The aim of this study was to investigate the expression of the CaSR in testicular tissue and sperm cells and the functional consequences of spermatozoid CaSR activation by calcimimetics. CaSR mRNA and protein were identified both in rat testicular tissue and in rat spermatozoa using real-time reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. Functionality of CaSR was evaluated by studying the influence of calcimimetic AMG 641 on rat and pig sperm motility. Treatment with AMG 641 100 nM for 1 hour increased rat sperm motility from a score of 1.0 ± 0.1 to 3.8 ± 0.3 (P < .05). AMG 641 also resulted in a modest but significant increase in the pig sperm motility parameters evaluated by computer-assisted sperm analysis. AMG 641 was effective in a wide range of concentrations but resulted in a more marked effect at 50-100 nM. In addition, AMG 641 did not have any negative effect on sperm viability, which was measured by flow cytometry. In conclusion, our results demonstrate the expression of functional CaSR in testicular tissue and sperm, which can be activated by calcimimetic AMG 641.

184 INHIBITION OF CALCIUM EFFLUX EXTENDS THE DURATION OF CALCIUM SIGNALS IN PIG OOCYTES

Calcium signaling involves the transient elevation in the intracellular free-calcium concentration, which is responsible for controlling a great number of biological functions. In many cell types, a signal is generated when calcium stored in the endoplasmic reticulum is released into the cytoplasm, followed by an influx of calcium across the plasma membrane. At the same time, calcium is removed from the cytosol by ATPases, which pump it back into the intracellular store or out of the cell. The size of the calcium signal is thus determined by the amount of calcium moving into and out of the cytoplasm. In the present study, we investigated the effect of inhibiting the movement of calcium across the plasma membrane on a calcium-signal that was artificially induced in pig oocytes. In vitro-matured pig oocytes were loaded with the calcium-indicator dye, fura-2. The release of calcium from the cytoplasmic stores was stimulated by adding ethanol at a final concentration of 7% and changes in the intracellular free-calcium levels were monitored by using InCyt Im2, a dual-wavelength fluorescence imaging system. In the control group, fluorescent measurements were performed in the presence of extracellular calcium. In additional treatment groups, the ethanol treatment was performed in (1) a calcium-free medium (prevents calcium influx); (2) the presence of 1 mM gadolinium (limits calcium fluxes across the plasma membrane in both directions); and (3) the presence of gadolinium in a calcium-free medium. In each group, 15 oocytes were measured; the data were subjected to 1-way ANOVA and differences between treatment means were compared by the Tukey's test. We found that in control oocytes, 7% ethanol induced a rise of 722.1 ± 49.2 nM in the cytoplasmic calcium levels and the average duration of the calcium transient was 309.1 ± 11.3 s. In the calcium-free medium, this increase was significantly smaller (only 117.9 ± 4.8 nM; P &lt; 0.01), probably because the calcium release was not followed by an influx of calcium across the plasma membrane. In the presence of 1 mM gadolinium in the regular calcium-containing medium, the intracellular calcium levels climbed by 278.8 ± 45.4 nM and dropped to baseline levels only after 773.3 ± 79.9 s. Finally, in the calcium-free medium and in the presence of 1 mM gadolinium, 7% ethanol induced only a small rise (64.5 ± 6.3 nM) in the cytoplasmic calcium levels. These latter increases were both significantly lower (P &lt; 0.01) compared to that in the control group. The results indicate that (1) intracellular calcium signals are sustained by a calcium influx from the extracellular medium and (2) preventing calcium efflux extends the duration of the cytoplasmic calcium elevation in the oocyte. This may have relevance in the manipulation of intracellular calcium levels in oocytes for the development of novel parthenogenetic activation methods.

Bradykinin promotes TLR2 expression in human gingival fibroblasts

Bradykinin (BK) is implicated in the sensation of pain, vasodilation, increases in vascular permeability and pathogenic processes associated with inflammation. Studies have shown that BK promotes the intracellular movement of calcium in human gingival fibroblasts by binding to the B2 receptor. In this study we investigated the effect of BK on regulation of Toll-like receptor 2 (TLR2) expression. Our results show that BK stimulates TLR2 receptor transcription and translation by activation of protein kinase C as well as AKT. Our study contributes important information on the regulation and expression of molecules that promote chronic inflammatory processes, which lead to periodontitis and consequently to loss of the dental organ.

2011 Award Recipients — William W. Schlaepfer, MD and Leroy R. Sharer, MD

FIGURE. No caption available. William W. Schlaepfer, MD, trained in pathology and neuropathology at the Yale Medical School where he conducted a doctoral thesis on Alzheimer Type 2 astrocytes during experimental ammonium intoxication in rats under the tutelage of Elias E. Manuelidis. He completed his training at the Max-Planck-Institut fur Psychiatrie in Munich, Germany, a Mecca for classic neuropathology. While in Munich, he became interested in the ultrastructure of peripheral nerve and the nature of the axonal cytoskeleton. He continued his experimental studies on peripheral nerve as staff neuropathologist at Cornell and Washington University medical schools where he introduced teased fiber analyses of nerve biopsies for differentiating demyelinating and axonal neuropathies and for semiquantitative assessment of Wallerian degeneration. Key insight into the nature of Wallerian degeneration derived from observations that the granular disintegration of axonal cytoskeleton was simulated when frozen sections of rat peripheral nerve were placed in Ringer's solution but not in isotonic saline. These observations led to a collaborative study with Richard Bunge in the Anatomy Department of Washington University showing that transected neurites of cultured dorsal root ganglia do not undergo Wallerian degeneration when calcium ions are removed from the media. Subsequent studies showed that granular disintegration of axonal cytoskeleton and fragmentation of myelin on teased fiber preparation could be prevented in transected and excised nerve when bathed in media lacking calcium ions. In pursuit of the calcium story, Dr Schlaepfer used a Research Career Development Award to spend a year in the laboratory of Peter Baker in Cambridge, England. The neurophysiology laboratories at Cambridge were world-renowned for Nobel laureate personages and their landmark discoveries of ion movements during nerve conduction in the giant axons of squid. Peter Baker was their leading authority on the movements of calcium. Dr Schlaepfer was, indeed, a small fish in a very …

Reciprocal Roles of Angiotensin II and Angiotensin II Receptors Blockade (ARB) in Regulating Cbfa1/RANKL via cAMP Signaling Pathway: Possible Mechanism for Hypertension-Related Osteoporosis and Antagonistic Effect of ARB on Hypertension-Related Osteoporosis

Hypertension is a risk factor for osteoporosis. Animal and epidemiological studies demonstrate that high blood pressure is associated with increased calcium loss, elevated parathyroid hormone, and increased calcium movement from bone. However, the mechanism responsible for hypertension-related osteoporosis remains elusive. Recent epidemiological studies indicate the benefits of Angiotensin II Receptors Blockade (ARB) on decreasing fracture risks. Since receptors for angiotensin II, the targets of ARB, are expressed in both osteoblasts and osteoclasts, we postulated that angiotensin II plays an important role in hypertension-related osteoporosis. Cbfa1 and RANKL, the important factors for maintaining bone homeostasis and key mediators in controlling osteoblast and osteoclast differentiation, are both regulated by cAMP-dependent signaling. Angiotensin II along with factors such as LDL, HDL, NO and homocysteine that are commonly altered both in hypertension and osteoporosis, can down-regulate the expression of Cbfa1 but up-regulate RANKL expression via the cAMP signaling pathway. We thus hypothesized that, by altering the ratio of Cbfa1/RANKL expression via the cAMP-dependent pathway, angiotensin II differently regulates osteoblast and osteoclast differentiation leading to enhanced bone resorption and reduced bone formation. Since ARB can antagonize the adverse effect of angiotensin II on bone by lowering cAMP levels and modifying other downstream targets, including LDL, HDL, NO and Cbfa1/RANKL, we propose the hypothesis that the antagonistic effects of ARB may also be exerted via cAMP signaling pathway.

The curative effect of zoledronic acid and pamidronic acid on treating ostealgia in malignant tumor with bone metastases and its side effects on serum calcium and phosphorus

Objective Bisphosphonates were widely used with the rate of malignant tumor with bone metastases increasing rapidly. The aim of this study was to evaluate zoledronic acid and pamidronic acid on treating ostealgia of malignant tumor with bone metastases and serum calcium, phosphorus and alkaline phosphorus movement.

Relaxation of intestinal smooth muscle and calcium movements.

Abstract The effects of papaverine, isoprenaline and N6,2′-O-dibutyryl 3′,5′-cyclic adenosine monophosphate (DiBu.C-AMP) on calcium movements in the taenia from the guinea-pig caecum have been investigated and compared with the effects of phenylephrine. Papaverine and DiBu.C-AMP antagonized the contraction of KCl-depolarized muscle induced by CaCl2 and increased 45Ca-efflux from the taenia. Papaverine also significantly depressed 45Ca-uptake by this preparation. These findings suggest that papaverine impairs the availability of calcium to the contractile system and that there may be a correlation between relaxation and increase of 45Ca-efflux. The action of DiBu.C-AMP resembles that of papaverine but its potency is less.

The influence of hexobarbitone on calcium ion movements in isolated heart muscle.

Abstract In beating atria (frequency 180/min) sodium hexobarbitone (7·8 × 10−4M) inhibited the rate of uptake of 45Ca2+ from the medium without influencing the total calcium content of the tissues. Concomitantly, the so-called exchangeable calcium fraction was diminished although not at equilbrium. In resting left auricles the barbiturate did not affect 45Ca+-uptake or the exchangeable calcium fraction. It seems likely that the barbiturate reduces membrane permeability towards Ca2+ during excitation without influencing the permeability at rest.

The Effect of Protoveratrine a on Potassium and Calcium Ion Movements in Muscle and Nerve

Abstract The effects of protoveratrine A on the efflux of potassium ions (K+) from frog and rat skeletal muscle and the isolated electrically driven rat heart have been studied. No effect was seen upon the rate of efflux from skeletal muscle but that from the heart was increased. Protoveratrine A increases K+ uptake from frog skeletal muscle and causes this tissue to release more calcium (Ca++). There was no increase in Ca++ release from lobster nerve treated with protoveratrine A. The theoretical implications of these findings are discussed.

Comparison of the effects of hydralazine and nifedipine on contractions and 45Ca influx of rat aorta

The effect of the vasodilator hydralazine has been compared with nifedipine on KCl-(K+) (60 mM) and noradrenaline-(NA) (10 microM) induced 45Ca uptake and contractile responses in rat aorta arterial strips without endothelium. Hydralazine (0.5-10 mM) was equally effective in relaxing K(+)- (IC50 = 2.2 +/- 0.17 mM) and NA- (IC50 = 3.06 +/- 0.25 mM) induced tension, the degree of relaxation depending on the dose. Nifedipine totally inhibited K(+)- (IC50 = 3.16 +/- 0.28 nM) induced contractions with lower doses than were necessary to relax (up to 54.0 +/- 4.1% with supramaximal concentrations) NA-induced contractions (IC50 = 1.48 +/- 0.12 microM). In the experiments in a calcium-free medium, nifedipine (1 microM) had no effect on the NA- (10 microM) induced contractions whereas hydralazine (1 mM) strongly inhibited them. Nifedipine did not affect the basal uptake of 45Ca but the induced uptakes were reduced to 66.3 +/- 3.2% (K+) and 65.5 +/- 4.1% (NA) of their basal values. Hydralazine did not affect the basal uptake of 45Ca nor that induced by the two vascoconstrictor agents. These results suggest that nifedipine acts on the cell membrane by blocking the movements of calcium through the voltage-dependent and receptor-operated calcium channels, whilst hydralazine has an intracellular effect.

Role of calcium in the analgesic action of tetrahydroisoxazolepyridinol and muscimol

The role of calcium in the analgesic activity of 4,5,6,7-tetrahydroisoxazole-(5,4-c) pyridin-2-ol (THIP) and muscimol has been investigated using the acetic acid assay procedure. THIP and muscimol produced significant analgesic response. Whilst neither calcium chloride nor nifedipine in the doses employed significantly altered the number of writhings, calcium chloride antagonized the analgesic responses of THIP and muscimol while nifedipine potentiated them. Similar responses were recorded for morphine. These findings suggest that THIP and muscimol, like morphine, might alter the calcium movements across the plasma membrane to elicit the analgesic response.

Relaxant effect of tetrazepam on rat uterine smooth muscle: role of calcium movement.

Tetrazepam is a benzodiazepine derivative clinically used as a muscle relaxant. The aim of the present work was to examine its effect on uterine smooth muscle of the rat in estrus. Tetrazepam required micromolar concentrations to relax contractile responses induced by KCl and acetylcholine in Ca2+ solution, but not oxytocin-induced contraction. In Ca(2+)-free solution, tetrazepam inhibited Ca(2+)-induced contractions in depolarized uterus and vanadate-induced contractions. We suggest that tetrazepam relaxes contractile responses induced by activation of voltage-sensitive calcium channels and receptor-operated calcium channels with little selectivity or that it antagonizes the effect of calcium at subsequent steps, possibly intracellular stores sensitive to vanadate but not sensitive to oxytocin. The inhibition of contraction of rat uterus is not related to high-affinity peripheral benzodiazepine binding sites.

Neuromuscular fatigue in healthy muscle: Underlying factors and adaptation mechanisms

Objectives This review aims to define the concept of neuromuscular fatigue and to present the current knowledge of the central and peripheral factors at the origin of this phenomenon. This review also addresses the literature that focuses on the mechanisms responsible for the adaption to neuromuscular fatigue. Method One hundred and eighty-two articles indexed in PubMed (1954–2010) have been considered. Results Neuromuscular fatigue has central and peripheral origins. Central fatigue, preponderant during long-duration, low-intensity exercises, may involve a drop in the central command (motor, cortex, motoneurons) elicited by the activity of cerebral neurotransmitters and muscular afferent fibers. Peripheral fatigue, associated with an impairment of the mechanisms from excitation to muscle contraction, may be induced by a perturbation of the calcium ion movements, an accumulation of phosphate, and/or a decrease of the adenosine triphosphate stores. To compensate for the consequent drop in force production, the organism develops several adaptation mechanisms notably implicating motor units. Conclusion Fatigue onset is associated with an alteration of the mechanisms involved in force production. Then, the interaction between central and peripheral mechanisms leads to a series of events that ultimately contribute to the observed decrease in force production.