Cumulative effects of H and P on force and power of skeletal muscle fibres from young and older adults.

The cellular causes of the age-related loss in power output and increased fatigability are unresolved. We previously observed that the depressive effects of hydrogen (H) (pH 6.2) and inorganic phosphate (P) (30 mm) did not differ in muscle fibres from young and older men.

Altered contractility, Ca transients, and cell morphology seen in a patient-specific iPSC-CM model of Ebstein's anomaly with left ventricular noncompaction.

Patients with two congenital heart diseases (CHDs), Ebstein's anomaly (EA) and left ventricular noncompaction (LVNC), suffer higher morbidity than either CHD alone. The genetic etiology and pathogenesis of combined EA/LVNC remain largely unknown. We investigated a familial EA/LVNC case associated with a variant (p.

Significance of α-Myosin Heavy Chain () Variants in Hypoplastic Left Heart Syndrome and Related Cardiovascular Diseases.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) with complex genetic inheritance. HLHS segregates with other left ventricular outflow tract (LVOT) malformations in families, and can present as either an isolated phenotype or as a feature of a larger genetic disorder. The multifactorial etiology of HLHS makes it difficult to interpret the clinical significance of genetic variants.

Clinical outcomes of temperature related injuries treated in the hospital setting, 2011-2018.

Background: Concerns over climate change have prompted substantial interest in temperature related injuries resulting from extreme weather conditions. Climate models predict that as global temperatures increase, the frequency and severity of extreme heat and cold weather events will grow which will likely increase the incidence of temperature related injury. The aim of this study was to analyze the healthcare impacts of temperature related injuries in the state of Illinois in order to serve as a model to guide future public health policy.

Contractility of Induced Pluripotent Stem Cell-Cardiomyocytes With an Head Domain Variant Associated With Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease; however, its etiology remains largely unknown. We previously demonstrated that genetic variants in the gene are significantly associated with HLHS. Additionally, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from an HLHS-affected family trio (affected parent, unaffected parent, affected proband) carrying an 6-R443P head domain variant demonstrated dysmorphic sarcomere structure and increased compensatory expression.

Ca dependency of limb muscle fiber contractile mechanics in young and older adults.

Age-induced declines in skeletal muscle contractile function have been attributed to multiple cellular factors, including lower peak force (P), decreased Ca sensitivity, and reduced shortening velocity (V). However, changes in these cellular properties with aging remain unresolved, especially in older women, and the effect of submaximal Ca on contractile function is unknown. Thus, we compared contractile properties of muscle fibers from 19 young (24 ± 3 yr; 8 women) and 21 older adults (77 ± 7 yr; 7 women) under maximal and submaximal Ca and assessed the abundance of three proteins thought to influence Ca sensitivity.

Cardiomyocyte slowly activating delayed rectifier potassium channel: regulation by exercise and β-adrenergic signaling.

Exercise training is known to prolong the ventricular cardiomyocyte action potential duration (APD), increasing Ca influx and contractility. The prolonged APD is caused, in part, by a decreased responsiveness to β-adrenergic agonists. The study's aims were to elucidate the mechanisms by which exercise training alters β-adrenergic regulation and to determine the involvement of delayed rectifier potassium channels ( and ) in the response.

Bioenergetic basis of skeletal muscle fatigue.

Energetic demand from high-intensity exercise can easily exceed ATP synthesis rates of mitochondria leading to a reliance on anaerobic metabolism. The reliance on anaerobic metabolism results in the accumulation of intracellular metabolites, namely inorganic phosphate (P) and hydrogen (H), that are closely associated with exercise-induced reductions in power. Cellular and molecular studies have revealed several steps where these metabolites impair contractile function demonstrating a causal role in fatigue.

Bioenergetic basis for the increased fatigability with ageing.

Key Points: The mechanisms for the age-related increase in fatigability during dynamic exercise remain elusive. We tested whether age-related impairments in muscle oxidative capacity would result in a greater accumulation of fatigue causing metabolites, inorganic phosphate (P ), hydrogen (H ) and diprotonated phosphate (H PO ), in the muscle of old compared to young adults during a dynamic knee extension exercise. The age-related increase in fatigability (reduction in mechanical power) of the knee extensors was closely associated with a greater accumulation of metabolites within the working muscle but could not be explained by age-related differences in muscle oxidative capacity.

Effects of regular exercise on ventricular myocyte biomechanics and K channel function.

Exercise training is known to protect the heart from ischemia and improve function during exercise by reducing cardiomyocyte action potential duration (APD) and increasing contractility. The cellular mechanisms involve β-adrenergic regulation and the ATP-sensitive K (K) channel, but how each alters function of the left ventricle and sex specificity is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to wheel-running (TRN) or sedentary (SED) groups.

Effects of elevated H and P on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans.

Key Points: The mechanisms responsible for the loss in muscle power and increased fatigability with ageing are unresolved. We show that the contractile mechanics of fibres from the vastus lateralis of old men were well-preserved compared to those of young men, but the selective loss of fast myosin heavy chain II muscle was strongly associated with age-related decrements in whole-muscle strength and power. We reveal that the combination of acidosis (H ) and inorganic phosphate (P ) is an important mediator of muscle fatigue in humans by inhibiting the low- to high-force state of the cross-bridge cycle and peak power, but the depressive effects of these ions on cross-bridge function were similar in fibres from young and old men.

Ventricular action potential adaptation to regular exercise: role of β-adrenergic and K channel function.

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K (K) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz.

Skeletal muscle PGC-1β signaling is sufficient to drive an endurance exercise phenotype and to counteract components of detraining in mice.

Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α and -1β serve as master transcriptional regulators of muscle mitochondrial functional capacity and are capable of enhancing muscle endurance when overexpressed in mice. We sought to determine whether muscle-specific transgenic overexpression of PGC-1β affects the detraining response following endurance training. First, we established and validated a mouse exercise-training-detraining protocol.

Calsequestrin depolymerizes when calcium is depleted in the sarcoplasmic reticulum of working muscle.

Calsequestrin, the only known protein with cyclical storage and supply of calcium as main role, is proposed to have other functions, which remain unproven. Voluntary movement and the heart beat require this calcium flow to be massive and fast. How does calsequestrin do it? To bind large amounts of calcium in vitro, calsequestrin must polymerize and then depolymerize to release it.

Muscle Fatigue from the Perspective of a Single Crossbridge.

The repeated intense stimulation of skeletal muscle rapidly decreases its force- and motion-generating capacity. This type of fatigue can be temporally correlated with the accumulation of metabolic by-products, including phosphate (Pi) and protons (H). Experiments on skinned single muscle fibers demonstrate that elevated concentrations of these ions can reduce maximal isometric force, unloaded shortening velocity, and peak power, providing strong evidence for a causative role in the fatigue process.

Treatment with ActRIIB-mFc Produces Myofiber Growth and Improves Lifespan in the Acta1 H40Y Murine Model of Nemaline Myopathy.

Nemaline myopathies (NMs) are a group of congenital muscle diseases caused by mutations in at least 10 genes and associated with a range of clinical symptoms. NM is defined on muscle biopsy by the presence of cytoplasmic rod-like structures (nemaline rods) composed of cytoskeletal material. Myofiber smallness is also found in many cases of NM and may represent a cause of weakness that can be counteracted by treatment.

Weekly versus monthly testosterone administration on fast and slow skeletal muscle fibers in older adult males.

Context: In older adults, loss of mobility due to sarcopenia is exacerbated in men with low serum T. T replacement therapy is known to increase muscle mass and strength, but the effect of weekly (WK) vs monthly (MO) administration on specific fiber types is unknown.

Objective: To determine the efficacy of WK vs MO T replacement on the size and functional capacity of individual fast and slow skeletal muscle fiber types.

Phosphate and acidosis act synergistically to depress peak power in rat muscle fibers.

Skeletal muscle fatigue is characterized by the buildup of H(+) and inorganic phosphate (Pi), metabolites that are thought to cause fatigue by inhibiting muscle force, velocity, and power. While the individual effects of elevated H(+) or Pi have been well characterized, the effects of simultaneously elevating the ions, as occurs during fatigue in vivo, are still poorly understood. To address this, we exposed slow and fast rat skinned muscle fibers to fatiguing levels of H(+) (pH 6.

Effects of low cell pH and elevated inorganic phosphate on the pCa-force relationship in single muscle fibers at near-physiological temperatures.

Intense muscle contraction induces high rates of ATP hydrolysis with resulting increases in Pi, H(+), and ADP, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.

Effects of prolonged space flight on human skeletal muscle enzyme and substrate profiles.

Our primary goal was to determine the effects of 6-mo flight on the International Space Station (ISS) on selected anaerobic and aerobic enzymes, and the content of glycogen and lipids in slow and fast fibers of the soleus and gastrocnemius. Following local anesthesia, biopsies were obtained from nine ISS crew members ∼45 days preflight and on landing day (R+0) postflight. We subdivided the crew into those who ran 200 min/wk or more (high treadmill, HT) in-flight from those who ran <100 min/wk (low treadmill, LT).

Confocal imaging of transmembrane voltage by SEER of di-8-ANEPPS.

Imaging, optical mapping, and optical multisite recording of transmembrane potential (V(m)) are essential for studying excitable cells and systems. The naphthylstyryl voltage-sensitive dyes, including di-8-ANEPPS, shift both their fluorescence excitation and emission spectra upon changes in V(m). Accordingly, they have been used for monitoring V(m) in nonratioing and both emission and excitation ratioing modes.

Skeletal muscle fatigue.

Skeletal muscle fatigue is defined as the fall of force or power in response to contractile activity. Both the mechanisms of fatigue and the modes used to elicit it vary tremendously. Conceptual and technological advances allow the examination of fatigue from the level of the single molecule to the intact organism.