Innervation Of Muscle Research Articles

Neural and contractile determinants of burst-like explosive isometric contractions of the knee extensors.

Walking and running are based on rapid burst-like muscle contractions. Burst-like contractions generate a Gaussian-shaped force profile, in which neuromuscular determinants have never been assessed. We investigated the neural and contractile determinants of the rate of force development (RFD) in burst-like isometric knee extensions. Together with maximal voluntary force (MVF), voluntary and electrically evoked (8 stimuli at 300 Hz, octets) forces were measured in the first 50, 100, and 150 ms of burst-like quadriceps contractions in 24 adults. High-density surface electromyography (HDsEMG) was adopted to measure the root mean square (RMS) and muscle fiber conduction velocity (MFCV) from the vastus lateralis and medialis. The determinants of voluntary force at 50, 100, and 150 ms were assessed by stepwise multiple regression analysis. Force at 50 ms was explained by RMS (R2 =0.361); force at 100 ms was explained by octet (R2 =0.646); force at 150 ms was explained by MVF (R2 =0.711) and octet (R2 =0.061). Peak RFD (which occurred at 60 ± 10ms from contraction onset) was explained by MVF (R2 =0.518) and by RMS50 (R2 =0.074). MFCV did not emerge as a determinant of RFD. Muscle excitation was the sole determinant of early RFD (50 ms), while contractile characteristics were more relevant for late RFD (≥100 ms). As peak RFD is mostly determined by MVF, it may not be more informative than MVF itself. Therefore, a time-locked analysis of RFD provides more insights into the neuromuscular characteristics of explosive contractions.

Understanding altered contractile properties in advanced age: insights from a systematic muscle modelling approach

Age-related alterations of skeletal muscle are numerous and present inconsistently, and the effect of their interaction on contractile performance can be nonintuitive. Hill-type muscle models predict muscle force according to well-characterised contractile phenomena. Coupled with simple, yet reasonably realistic activation dynamics, such models consist of parameters that are meaningfully linked to fundamental aspects of muscle excitation and contraction. We aimed to illustrate the utility of a muscle model for elucidating relevant mechanisms and predicting changes in output by simulating the individual and combined effects on isometric force of several known ageing-related adaptations. Simulating literature-informed reductions in free Ca2+ concentration and Ca2+ sensitivity generated predictions at odds qualitatively with the characteristic slowing of contraction speed. Conversely, incorporating slower Ca2+ removal or a fractional increase in type I fibre area emulated expected changes; the former was required to simulate slowing of the twitch measured experimentally. Slower Ca2+ removal more than compensated for force loss arising from a large reduction in Ca2+ sensitivity or moderate reduction in Ca2+ release, producing realistic age-related shifts in the force-frequency relationship. Consistent with empirical data, reductions in free Ca2+ concentration and Ca2+ sensitivity reduced maximum tetanic force only slightly, even when acting in concert, suggesting a modest contribution to lower specific force. Lower tendon stiffness and slower intrinsic shortening speed slowed and prolonged force development in a compliance-dependent manner without affecting force decay. This work demonstrates the advantages of muscle modelling for exploring sources of variation and identifying mechanisms underpinning the altered contractile properties of aged muscle.

Preparation and assessment of an optimized multichannel acellular nerve allograft for peripheral nerve regeneration.

Peripheral nerve regeneration after injury is still a clinical problem. The application of autologous nerve grafting, the gold standard treatment, is greatly restricted. Acellular nerve allografts (ANAs) are considered promising alternatives, but they are difficult to achieve satisfactory therapeutic outcomes, which may be attributed to their compact inherent ultrastructure and substantial loss of extracellular matrix (ECM) components. Regarding these deficiencies, this study developed an optimized multichannel ANA by a modified decellularization method. These innovative ANAs were demonstrated to retain more ECM bioactive molecules and regenerative factors, with effective elimination of cellular antigens. The presence of microchannels with larger pore size allowed ANAs to gain higher porosity and better swelling performance, which improves their internal ultrastructure. Their mechanical properties were more similar to those of native nerves. Moreover, the optimized ANAs exhibited good biocompatibility and possessed significant advantages in supporting the proliferation and migration of Schwann cells in vitro. The in vivo results further confirmed their superior capacity to promote axon regrowth and myelination as well as restore innervation of target muscles, leading to better functional recovery than the conventional ANAs. Overall, this study demonstrates that the optimized multichannel ANAs have great potential for clinical application and offer new insight into the further improvement of ANAs.

Increased TMEM16A-Mediated Ca2+-Activated Cl- Currents in Portal Vein Smooth Muscle Cells of Caveolin 1-Deficient Mice.

Ca2+-activated Cl- (ClCa) channels regulate membrane excitability and myogenic tone in vascular smooth muscles. TMEM16A-coding proteins are mainly responsible for functional ClCa channels in vascular smooth muscles, including portal vein smooth muscles (PVSMs). Caveolae are cholesterol-rich and Ω-shaped invaginations on the plasma membrane that structurally contributes to effective signal transduction. Caveolin 1 (Cav1) accumulates in caveolae to form functional complexes among receptors, ion channels, and kinases. The present study examined the functional roles of Cav1 in the expression and activity of ClCa channels in the portal vein smooth muscle cells (PVSMCs) of wild-type (WT) and Cav1-knockout (KO) mice. Contractile experiments revealed that the amplitude of spontaneous PVSM contractions was larger in Cav1-KO mice than WT mice. Under whole-cell patch-clamp configurations, ClCa currents were markedly inhibited by 1 µM Ani9 (a selective TMEM16A ClCa channel blocker) in WT and Cav1-KO PVSMCs. However, Ani9-sensitive ClCa currents were significantly larger in Cav1-KO PVSMCs than in WT PVSMCs. Expression analyses showed that TMEM16A expression levels were higher in Cav1-KO PVSMs than in WT PVSMs. Therefore, the caveolar structure formed by Cav1 negatively regulates the expression and activity of TMEM16A-mediated ClCa channels in vascular smooth muscle cells.

Acute, Non-Specific Low Back Pain Does Not Impair Isometric Deadlift Force or Electromyographic Excitation: A Cross-Sectional Study.

Low back pain (LBP) is a leading cause of disability. The use of deadlift-based assessments in assessing LBP is becoming common in clinical settings, but these concepts have not been well studied. We sought to compare force and muscle excitation during isometric deadlifts in participants suffering from LBP versus asymptomatic controls. We also compared these outcomes for conventional versus hexagonal barbells. Sixteen adults with mild-to-moderate, acute, non-specific LBP and 19 controls performed maximal, isometric deadlifts while standing on a force plate using conventional and hexagonal barbells. Surface electromyographic signals were recorded from the upper trapezius, external oblique, erector spinae, vastus lateralis, and biceps femoris. Normalized peak force and peak rate of force development were similar for those with acute, non-specific LBP and controls. Surface electromyographic excitation was not different between groups, but was higher with the hexagonal barbell for the vastus lateralis and upper trapezius. Both groups felt equally safe and confident. In summary, the presence of acute, non-specific LBP did not impair peak and rapid force or muscle excitation. Hexagonal barbells may optimize knee extensor and trapezius activation. Deadlift-based force assessments appear safe and may be useful in the assessment of functional strength in patients with acute, non-specific LBP.

A comprehensive anatomical classification system of the extramuscular innervation of the gracilis muscle as guidance for free functional muscle transfer

PurposeThe gracilis muscle is one of the most frequently used muscles in reconstructive surgeries. It can be utilized as both less complex flaps and a free functional muscle flap to restore function to other muscles. As little is known of the precise extramuscular innervation of the gracilis muscle, the present study performs an accurate assessment to provide as much important anatomical information for clinicians as possible. Material and methodsA classical anatomical dissection was performed on eighty-five lower limbs (45 right, 40 left) fixed in 10% formalin solution. The variability in the extramuscular innervation of the gracilis muscle was assessed. Some morphometric measurements were collected. ResultsA four-fold classification of extramuscular innervation was created for the gracilis muscle. Type I (64.7%), the most frequent type, presented at least one proximal nerve branch. Type II (25.9%) lacked this branch. Type III (8.2%) possessed an additional neural supply from the muscular nerve branch innervating the adductor longus muscle. Type IV (1.2%) was similar to Type III, but the additional neural supply originated from the muscular nerve branch innervating the adductor magnus muscle. ConclusionClear anatomical variability was noted for extramuscular innervation of the gracilis muscle. All the presented Types seem to be suitable for splitting a muscle belly and use its part in free functional muscle transfer. However, it appears that Type III and IV may ease this procedure, because of the additional nerve branches. This classification system can deliver important information for clinicians performing complex reconstructive surgeries with the use of the gracilis muscle.

An assessment of the variation of the intramuscular innervation of the gracilis muscle, with the aim of determining its neuromuscular compartments.

Some muscles present neuromuscular compartments, one of which is the gracilis muscle. The aim of the present study is to determine the number of compartments present within the gracilis muscle based on its intramuscular innervation patterns; such knowledge could be of value in free functional muscle transfer. The study comprised 72 gracilis muscles (38 women, 34 men), fixed in 10% formalin solution. The muscles were removed and then stained using Sihler's method. When sufficient transparency was achieved, some measurements were made. Three different types of intramuscular innervation were distinguished. Type I (70.8%) was featured by at least one direct proximal nerve branch. Type II (23.6%) presented at least one indirect proximal nerve branch. Type III (5.6%) did not possess any proximal nerve branch. The median of descended nerve branches was five. Considerable anatomical variation is possible within the intramuscular innervation of the gracilis muscle. The muscle presents neuromuscular compartments, but the exact number depends on the type of its intramuscular innervation and the number of the main descendent nerve branches. All three types seem to be appropriate for free functional muscle transfer. Our findings may be of great value for surgeons carrying out complex reconstructions with the use of the gracilis muscle.

Outcome of using the spinal accessory nerve for functional muscle innervation in facial paralysis reconstruction: The first two cases in Vietnam and literature review

Abstract Facial nerve injuries with various causes, such as after trauma, tumor dissection, radiotherapy, etc., resulting the patient's functional, aesthetic, and psychological sequelae. For many decades, plastic surgeons have introduced numerous different nerve sources to overcome the above sequelae, such as contralateral facial nerve, the hypoglosal nerve, the masseter nerve, and the spinal accessory nerve (CN XI). There were various advantages and disadvantages of donor nerves sources. However, the use of ipsilateral donor nerve is said to have many benefits. In this report, we would like to present preliminary results of using the CN XI source in treatment of subacute and chronic VII nerve injury. These were the first two cases of successful surgery using this nerve source in Vietnam. Keywords: Facial nerve injury, facial paralysis, nerve transfer, spinal accessory nerve.

Effect of standardized training in combination with masseter sensitization on corticomotor excitability in bruxer and control individuals: a proof of concept study

Recently, it has been proposed that bruxism could represent an overlearned behavior due to the absence of corticomotor plasticity following a relevant tooth-clenching task (TCT). This study assessed the modulatory effects of a nerve growth factor (NGF) injection on masseter muscle corticomotor excitability, jaw motor performance, pain, and limitation in bruxer and control participants following a TCT. Participants characterized as definitive bruxers or controls were randomly assigned to have injected into the right masseter muscle either NGF or isotonic saline (IS), resulting in a study with 4 arms: IS_Control (n = 7), IS_Bruxer (n = 7); NGF_Control (n = 6), and NGF_Bruxer (n = 8). The primary outcome was the masseter motor evoked potential (MEP) amplitude measured at baseline and after a TCT. After the interventions, significantly higher and lower MEP amplitude and corticomotor map area were observed, respectively, in the IS_Control and NGF_Control groups (P < 0.05). Precision and accuracy depended on the series and target force level with significant between-group differences (P < 0.01). NGF‐induced masseter muscle sensitization, in combination with a training-induced effect, can significantly impact the corticomotor excitability of the masseter muscle in control participants indicating substantial changes in corticomotor excitability, which are not observed in bruxers. These preliminary findings may have therapeuthic implications for the potential to “detrain” and manage bruxism, but further studies with larger sample sizes will be needed to test this new concept.

The effect of thymol on acetylcholine-induced contractions of the rat ileum and uterus under ex vivo conditions.

Thyme (Thymus vulgaris L.) is a well-known medicinal plant, the aerial parts of which have long been used internally or externally as a traditional remedy for various diseases. Thyme essential oils have important pharmaceutical applications and are regularly used in the pharmaceutical, food and cosmetic industries. In folk medicine, thyme preparations are used to treat respiratory, digestive, cardiovascular and nervous disorders, as well as to relieve dysmenorrhea. Thymol, a major constituent of Thymus vulgaris essential oil, has been shown to affect skeletal and smooth muscle excitation and contraction. Therefore, the main objective of this study was to evaluate its effect on acetylcholine (ACh)-induced rat intestinal and uterine preparations. Isolated ileum and uterine horn preparations were placed in a 20-ml organ bath containing Tyrode or De Jalon solution and exposed to graded concentrations of ACh (0.036, 0.109, 0.36, 1.09, 3,6, 10.9, and 36μM) and either 0.02 or 0.2mM thymol. Additionally, the dose-response relationship of thymol impact on intestinal and uterine contraction was evaluated. Contraction changes were monitored using an isometric transducer. Thymol at the higher dose (0.2mM) significantly reduced ACh-induced intestinal and uterine contractions. Thus, this study provides new important data on competitive actions between thymol and ACh. In the dose-response study, the IC50 values were calculated as 5.26mM for the ileum and 5.35mM for the uterus. Our results demonstrated the efficacy of thymol in reducing ileal and uterine smooth muscle contractions, thus supporting the use of thyme in traditional medicine in the treatment of digestive disorders and painful menstrual cramps.

A rare anatomical star shaped branching pattern of spinal accessory nerve: A case report with review of literature

The spinal accessory nerve provides motor innervation to the sternocleidomastoid and trapezius muscle. It is an extremely important structure to be preserved during neck dissection to avoid sequalae related to shoulder dysfunctions. The incidence of shoulder dysfunction and morbidity can be attributed to varied anatomy and branching pattern of the nerve or the contribution by the cervical plexus to the motor innervations of the trapezius muscle. Hence it is important to have knowledge of the varied anatomy and branching pattern of the spinal accessory nerve to avoid the possible shoulder morbidity and dysfunction following neck dissections. Lanisnik B etal’s study showed that there are three recognizable branching patterns of the spinal accessory nerve for innervation of the trapezius muscle. In type 1, the SAN enters the Sternocleidomastoid muscle and a single trapezius muscle branch exits from the posterior border of the SCM after receiving communications from the cervical nerves, especially C2 and C3. In type 2, the motor branch for trapezius muscle separates from the main trunk at level II, before the nerve enters the sternocleido-mastoid muscle. In the type 3 pattern, CN XI enters the SCM in the same way as described in type 1, and the motor branch for the trapezius muscle exits from the SCM muscle behind its posterior border; however, it does not immediately travel to level V and the trapezius muscle, but instead takes a more medial course and mixes with the cervical nerves, predominantly C2 and C3. In this case report, we will discuss an unusual branching pattern of spinal accessory nerve similar to the type 3 variant as explained by Lanisnik that we have encountered during a modified radical neck dissection, in a case of Squamous cell carcinoma of right buccal mucosa.

Targeted Muscle Reinnervation for Treatment of Postresection Interdigital Neuroma: A Cadaveric Feasibility Study.

Symptomatic postresection interdigital neuroma is a frustrating problem that causes debilitating foot pain. Implementing the concepts of targeted muscle innervation, this study offers a novel nerve transfer involving the resected third common plantar digital nerve (CPDN) to the motor nerve branch of the third dorsal interosseous muscle (DIMB) to improve postresection pain. Ten fresh feet from seven cadaveric donors were used for this study. CPDN and DIMB lengths and diameters were measured, along with nerve overlap after the transfer with ankle in neutral position and in maximal dorsiflexion. Motor entry point to the calcaneal tuberosity and to the fifth metatarsal tuberosity were measured and used to evaluate the ratio relative to foot length. Means, standard deviations, and P values were calculated for each measure and between sexes and feet (right and left). In all specimens, the nerve transfer was technically feasible, without notable size mismatch between the donor and recipient nerves. CPDN, DIMB, and important anatomical reference points were identifiable in all specimens. Average CPDN length was 30.1 ± 8.2 mm. The average DIMB length was 14.4 ± 3.9 mm. The overlap between the donor and recipient in neutral ankle position at the transfer site was 6.4 ± 1.8 mm. Given their anatomical locations, a nerve transfer between the third CPDN and third DIMB is surgically feasible. This novel technique is a viable option that can be used instead of the conventional technique of muscle implantation or more proximal re-resection for symptomatic postresection interdigital neuroma.

Evaluation of musculoskeletal models, scaling methods, and performance criteria for estimating muscle excitations and fiber lengths across walking speeds.

Muscle-driven simulations have been widely adopted to study muscle-tendon behavior; several generic musculoskeletal models have been developed, and their biofidelity improved based on available experimental data and computational feasibility. It is, however, not clear which, if any, of these models accurately estimate muscle-tendon dynamics over a range of walking speeds. In addition, the interaction between model selection, performance criteria to solve muscle redundancy, and approaches for scaling muscle-tendon properties remain unclear. This study aims to compare estimated muscle excitations and muscle fiber lengths, qualitatively and quantitatively, from several model combinations to experimental observations. We tested three generic models proposed by Hamner et al., Rajagopal et al., and Lai-Arnold et al. in combination with performance criteria based on minimization of muscle effort to the power of 2, 3, 5, and 10, and four approaches to scale the muscle-tendon unit properties of maximum isometric force, optimal fiber length, and tendon slack length. We collected motion analysis and electromyography data in eight able-bodied subjects walking at seven speeds and compared agreement between estimated/modelled muscle excitations and observed muscle excitations from electromyography and computed normalized fiber lengths to values reported in the literature. We found that best agreement in on/off timing in vastus lateralis, vastus medialis, tibialis anterior, gastrocnemius lateralis, gastrocnemius medialis, and soleus was estimated with minimum squared muscle effort than to higher exponents, regardless of model and scaling approach. Also, minimum squared or cubed muscle effort with only a subset of muscle-tendon unit scaling approaches produced the best time-series agreement and best estimates of the increment of muscle excitation magnitude across walking speeds. There were discrepancies in estimated fiber lengths and muscle excitations among the models, with the largest discrepancy in the Hamner et al. model. The model proposed by Lai-Arnold et al. best estimated muscle excitation estimates overall, but failed to estimate realistic muscle fiber lengths, which were better estimated with the model proposed by Rajagopal et al. No single model combination estimated the most accurate muscle excitations for all muscles; commonly observed disagreements include onset delay, underestimated co-activation, and failure to estimate muscle excitation increments across walking speeds.

Differences between vastus medialis and lateralis excitation onsets are dependent on the relative distance of surface electrodes placement from the innervation zone location

Conflictual results between the onset of vastus medialis (VM) and vastus lateralis (VL) excitation may arise from methodological aspects related to the detection of surface electromyograms. In this study we used an array of surface electrodes to assess the effect of detection site, relative to the muscle innervation zone, on the difference between VM and VL excitation onsets. Ten healthy males performed moderate isometric knee extension at 40 % of their maximal voluntary isometric contraction. After the actual VM-VL onset was defined (estimated when action potentials were generated at the neuromuscular junctions of both muscles), we calculated the largest bias that the detection site may introduce in the VM-VL onset estimation. We also assessed whether the location often considered for positioning bipolar electrodes on each muscle leads to VM-VL onset estimations comparable to the actual VM-VL onset. Our main results revealed that a maximum absolute bias of 20.48 ms may be introduced in VM-VL onset estimations due to the electrodes’ detection site. In addition, mean differences of ∼ 12 ms in VM-VL onset estimations were attributable to largest possible discrepancies in the paired position of channels with respect to the innervation zone for VL and VM. When considering the classical location for positioning the bipolar electrodes over these muscles, differences error was subtle (∼3.4 ms) when compared with the actual VM-VL onset. Nonetheless, when accounting for the effect of relative differences in electrode position between muscles is not possible, our results suggest that a systematic absolute error of ∼ 12 ms should be considered in future studies regarding VM-VL onset estimations, suggesting that onset differences lower than that might not be clinically relevant.

Phenotype, genotype, and management of congenital fibrosis of extraocular muscles type 1 in 16 Chinese families

PurposeCongenital fibrosis of extraocular muscles type 1 (CFEOM1), a classical subtype of CFEOM, is characterized by restrictive ophthalmoplegia and ptosis. It is mainly caused by aberrant neural innervation of the extraocular muscles. This study aimed to investigate the genetic characteristics and clinical manifestations of CFEOM1 in Chinese families.MethodsThe clinical data, including ocular examinations, magnetic resonance imaging (MRI), and surgical procedures of affected individuals from 16 Chinese CFEOM1 families, were collected. The genomic DNA of 16 probands and their family members were sequenced for causative KIF21A gene mutations. Linkage analysis using microsatellite markers across KIF21A was also conducted.ResultsAffected individuals were presented with bilateral non-progressive ptosis, restricted horizontal eye movement, fixed infraduction of both eyes, compensatory chin-up head position, and neuromuscular abnormalities. Three heterozygous KIF21A mutations, c.2860C > T (p.R954W) (in eight families), c.2861G > T (p.R954L) (in two families), and c.2861G > A (p.R954Q) (in two families) were identified, which implied that hotspot mutations were common in Chinese CFEOM1 families. Germline Mosaicism was likely to be the cause of affected individuals with asymptomatic parents without KIF21A mutations presented in the eight families. Two affected individuals underwent modified levator muscle complex suspension surgery and achieved a good result without any complications.ConclusionInstead of evaluating the whole CFEOM1 gene variant, hotspot mutations could be given priority for screening. The occurrence of germline mosaicism has to be taken into account in genetic counseling. Patients with CFEOM1 who have ptosis may benefit from an innovative surgical procedure called modified levator muscle complex suspension.

Blockage of neuromuscular glutamate receptors impairs reinnervation following nerve crush in adult mice.

Motor axons in peripheral nerves are capable of regeneration following injury. However, complete recovery of motor function is rare, particularly when reinnervation is delayed. We have previously found that glutamate receptors play a crucial role in the successful innervation of muscle during mouse development. In particular, blocking N-methyl-D-aspartate (NMDA) receptor activity delays the normal elimination of excess innervation of each neuromuscular junction. Here, we use behavioral, immunohistochemical, electrophysiological, and calcium imaging methods to test whether glutamate receptors play a similar role in the transition from polyneuronal to mono-innervation and in recovery of function following peripheral nerve injury in mature muscle.

Brainstem noradrenergic neurons: Identifying a hub at the intersection of cognition, motility, and skeletal muscle regulation.

Brainstem noradrenergic neuron clusters form a node integrating efferents projecting to distinct areas such as those regulating cognition and skeletal muscle structure and function, and receive dissimilar afferents through established circuits to coordinate organismal responses to internal and environmental challenges. Genetic lineage tracing shows the remarkable heterogeneity of brainstem noradrenergic neurons, which may explain their varied functions. They project to the locus coeruleus, the primary source of noradrenaline in the brain, which supports learning and cognition. They also project to pre-ganglionic neurons, which lie within the spinal cord and form synapses onto post-ganglionic neurons. The synapse between descending brainstem noradrenergic neurons and pre-ganglionic spinal neurons, and these in turn with post-ganglionic noradrenergic neurons located at the paravertebral sympathetic ganglia, support an anatomical hierarchy that regulates skeletal muscle innervation, neuromuscular transmission, and muscle trophism. Whether any noradrenergic neuron subpopulation is more susceptible to damaged protein deposit and death with ageing and neurodegeneration is a relevant question that answer will help us to detect neurodegeneration at an early stage, establish prognosis, and anticipate disease progression. Loss of muscle mass and strength with ageing, termed sarcopenia, may predict impaired cognition with ageing and neurodegeneration and establish an early time to start interventions aimed at reducing central noradrenergic neurons hyperactivity. Complex multidisciplinary approaches, including genetic tracing, specific circuit labelling, optogenetics and chemogenetics, electrophysiology, and single-cell transcriptomics and proteomics, are required to test this hypothesis pre-clinical.

CHRNA1 induces sarcopenia through neuromuscular synaptic elimination.

Sarcopenia seriously affects the quality of life of the elderly, but its molecular mechanism is still unclear. Degeneration in muscle innervation is related to age-related movement disorders and muscle atrophy. The expression of CHRNA1 is increased in the skeletal muscle of the elderly, and in aging rodents. Therefore, we investigated whether CHRNA1 induces the occurrence and development of sarcopenia. Compared with the control group, local injection of AAV9-CHRNA1 into the hindlimb muscles decreased the percentage of muscle innervation. At the same time, the skeletal muscle mass decreased, as manifested by a decrease in the gastrocnemius mass index and the cross-sectional area of the muscle fibers. The function of skeletal muscle also decreased, which was manifested by decreases of compound muscle action potential and muscle contractility. Therefore, we concluded that upregulation of CHRNA1 can induce and aggravate sarcopenia.

Targeted transcript analysis in muscles from patients with genetically diverse congenital myopathies.

Congenital myopathies are a group of early onset muscle diseases of variable severity often with characteristic muscle biopsy findings and involvement of specific muscle types. The clinical diagnosis of patients typically relies on histopathological findings and is confirmed by genetic analysis. The most commonly mutated genes encode proteins involved in skeletal muscle excitation–contraction coupling, calcium regulation, sarcomeric proteins and thin–thick filament interaction. However, mutations in genes encoding proteins involved in other physiological functions (for example mutations in SELENON and MTM1, which encode for ubiquitously expressed proteins of low tissue specificity) have also been identified. This intriguing observation indicates that the presence of a genetic mutation impacts the expression of other genes whose product is important for skeletal muscle function. The aim of the present investigation was to verify if there are common changes in transcript and microRNA expression in muscles from patients with genetically heterogeneous congenital myopathies, focusing on genes encoding proteins involved in excitation–contraction coupling and calcium homeostasis, sarcomeric proteins, transcription factors and epigenetic enzymes. Our results identify RYR1, ATPB2B and miRNA-22 as common transcripts whose expression is decreased in muscles from congenital myopathy patients. The resulting protein deficiency may contribute to the muscle weakness observed in these patients. This study also provides information regarding potential biomarkers for monitoring disease progression and response to pharmacological treatments in patients with congenital myopathies.

Ion channel molecular complexes in vascular smooth muscle.

Ion channels that influence membrane potential and intracellular calcium concentration control vascular smooth muscle excitability. Voltage-gated calcium channels (VGCC), transient receptor potential (TRP) channels, voltage (KV), and Ca2+-activated K+ (BK) channels are key regulators of vascular smooth muscle excitability and contractility. These channels are regulated by various signaling cues, including protein kinases and phosphatases. The effects of these ubiquitous signaling molecules often depend on the formation of macromolecular complexes that provide a platform for targeting and compartmentalizing signaling events to specific substrates. This manuscript summarizes our current understanding of specific molecular complexes involving VGCC, TRP, and KV and BK channels and their contribution to regulating vascular physiology.