In skeletal muscles, acetylcholine is released by nerve terminals at the motor end plate-the point of synaptic communication between motor neurons and muscle fibers. Binding of acetylcholine to its receptors on the sarcolemma allows entry of sodium ions into the cell and triggers an action potential in the muscle cell. Thus, electrical signals from the brain are transmitted to the muscle. Subsequently, the enzyme acetylcholinesterase breaks down acetylcholine to prevent excessive muscle stimulation. Individuals with the disorder myasthenia gravis, develop antibodies against the acetylcholine receptor. This prevents transmission of electrical signals between the motor neuron and muscle fiber and impairs skeletal muscle contraction. Myasthenia gravis is treated using drugs that inhibit acetylcholinesterase (allowing more opportunities for the neurotransmitter to stimulate the remaining receptors) or suppress the immune system (preventing the formation of antibodies). Unlike skeletal muscles, smooth muscles present in the walls of internal organs are innervated by the autonomic nervous system and undergo involuntary contractions. Contraction is mediated by the interaction between two filament proteins-actin and myosin. The interaction of actin and myosin is closely linked to intracellular calcium concentration. In response to neurotransmitter or hormone sig…
Skeletal muscles continuously produce ATP to provide the energy that enables muscle contractions. Skeletal muscle fibers can be categorized as type I, type IIA, or type IIB based on differences in their contraction speed and how they produce ATP, as well as physical differences related to these factors. Most human muscles contain all three muscle fiber types, albeit in varying proportions. Type I, or slow oxidative, muscle fibers appear red due to large numbers of capillaries and high levels of myoglobin, an oxygen-storing protein. Type I muscle fibers contain more mitochondria, which produce ATP through oxidative phosphorylation, than type II fibers. Slow oxidative muscle fibers use aerobic respiration, involving oxygen and glucose, to produce ATP. In addition to contracting more slowly than type II fibers, type I fibers receive nerve signals more slowly, contract for longer periods, and are more resistant to fatigue. Type I fibers primarily store energy as fatty substances called triglycerides. Type II, or fast, muscle fibers often appear white. Relative to type I fibers, type II fibers receive nerve signals and contract more quickly, but contract for shorter periods and fatigue more quickly. Type II muscle fibers primarily store energy as ATP and creatine phosphate. Type IIA, or fast oxidative, muscle fibers primarily u…
Skeletal muscle is the most abundant type of muscle in the body. Tendons are the connective tissue that attaches skeletal muscle to bones. Skeletal muscles pull on tendons, which in turn pull on bones to carry out voluntary movements.
Skeletal muscles are surrounded by a layer of connective tissue called epimysium, which helps protect the muscle. Beneath the epimysium, an additional layer of connective tissue, called perimysium, surrounds and groups together subunits of skeletal muscle called fasciculi. Each fascicle is a bundle of skeletal muscle cells, or myocytes, which are often called skeletal muscle fibers due to their size and cylindrical appearance. Between the muscle fibers is an additional layer of connective tissue called endomysium. The muscle fiber membrane is called the sarcolemma. Each muscle fiber is made up of multiple rod-like chains called myofibrils, which extend across the length of the muscle fiber and contract. Myofibrils contain subunits called sarcomeres, which are made up of actin and myosin in thin and thick filaments, respectively. Actin contains myosin-binding sites that allow thin and thick filaments to connect, forming cross bridges. For a muscle to contract, accessory proteins that cover myosin-binding sites on thin filaments must be displaced to enable the formation of cross bridges. During muscle contracti…
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
When ATP, that is attached to the myosin head, is hydrolyzed to ADP, myosin moves into a high energy state bound to actin, creating a cross-bridge. When ADP is released, the myosin head moves to a low energy state, moving actin toward the center of the sarcomere. Binding of a new ATP molecule dissociates myosin from actin. When this ATP is hydrolyzed, the myosin head will bind to actin, this time on a portion of actin closer to the end of the sarcomere. Regulatory proteins troponin and tropomyosin, along with calcium, work together to control the myosin-actin interaction. When troponin binds to calcium, tropomyosin is moved away from the myosin-binding site on actin, allowing myosin and actin to interact and muscle contraction to occur. As a regulator of muscle contraction, calcium concentration is very closely controlled in muscle fibers. Muscle fibers are in close contact with motor neurons. Action potentials in motor neurons cause the release of the neurotransmitter acetylcholine in the vicinity of muscle fibers. This ge…
Source:Tracey A. Milligan, MD; Tamara B. Kaplan, MD; Neurology, Brigham and Women's/Massachusetts General Hospital, Boston, Massachusetts, USA
There are two main types of reflexes that are tested on a neurological examination: stretch (or deep tendon reflexes) and superficial reflexes. A deep tendon…
The cytoplasm consists of organelles, an aqueous solution called the cytosol, and a framework of protein scaffolds called the cytoskeleton. The cytosol is a rich broth of ions, small organic molecules such as glucose, and macromolecules such as proteins. Several cellular processes including protein synthesis occur in the cytoplasm.
The composition of the cytosol promotes protein folding such that hydrophobic amino acid side chains are oriented away from the aqueous solution and towards the protein core. However, cellular stressors such as aging and changes in pH, temperature, or osmolarity cause protein misfolding. Misfolded proteins may aggregate to form insoluble deposits in the cytoplasm. Insoluble protein aggregates are implicated in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. The eukaryotic cytoskeleton consists of three types of filamentous proteins: microtubules, microfilaments, and intermediate filaments. Microtubules–the largest type of filament–are made up of the protein tubulin. Microtubules are dynamic structures that can grow or shrink by adding or removing tubulin molecules from the ends of their strands. They provide structural stability and provide tracks for the transport of proteins and vesicles within the cell. In addition, microtubules play a…
The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repel substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In the process of facilitated transport, also known as facilitated diffusion, molecules and ions travel across a membrane via two types of membrane transport proteins: channels and carrier proteins. These membrane transport proteins enable diffusion without requiring additional energy. Channel proteins form a hydrophilic pore through which charged molecules can pass through, thus avoiding the hydrophobic layer of the membrane. Channel proteins are specific for a given substance. For example, aquaporins are channel proteins that specifically facilitate the transport of water through the plasma membrane. Channel proteins are either always open or gated by some mechanism to control flow. Gated channels remain closed until a particular ion or substance binds to the channel, or some other mechanism occurs. Gated channels are found in the membranes of cells such as muscle cells and nerve cells. Muscle contractions occur when the relative concentrations of ions on the interior and…
The parasympathetic nervous system is one of the two major divisions of the autonomic nervous system. This parasympathetic system is responsible for regulating many unconscious functions, such as heart rate and digestion. It is composed of neurons located in both the brain and the peripheral nervous system that send their axons to target muscles, organs, and glands.
Activation of the parasympathetic system tends to have a relaxing effect on the body, promoting functions that replenish resources and restore homeostasis. It is therefore sometimes referred to as the “rest and digest” system. The parasympathetic system predominates during calm times when it is safe to devote resources to basic “housekeeping” functions without a threat of attack or harm. The parasympathetic nervous system can be activated by various parts of the brain, including the hypothalamus. Preganglionic neurons in the brainstem and sacral part of the spinal cord first send their axons out to ganglia—clusters of neuronal cell bodies—in the peripheral nervous system. These ganglia contain the connections between pre- and postganglionic neurons and are located near the organs or glands that they control. From here, postganglionic neurons send their axons onto target tissues—generally smooth muscle, cardiac muscle, or glands. Typic…
Ion channels maintain the membrane potential of a cell. For most cells, especially excitable ones, the inside has a more negative charge than the outside of the cell, due to a greater number of negative ions than positive ions. For excitable cells, like firing neurons, contracting muscle cells, or sensory touch cells, the membrane potential must be able to change rapidly moving from a negative membrane potential to one that is more positive. To achieve this, cells rely on two types of ion channels: ligand-gated and voltage-gated. Ligand-gated ion channels, also called ionotropic receptors, are transmembrane proteins that form a channel but which also have a binding site. When a ligand binds to the surface, it opens the ion channel. Common ionotropic receptors include the NMDA, kainite, and AMPA glutamate receptors and the nicotinic acetylcholine receptors. When a ligand, like glutamate or acetylcholine, binds to its receptor it allows the influx of sodium (Na+) and calcium (Ca++) ions into the cells. The positive ions, or cations, follow down their electrochemical gradient, moving from the more positive extracellular surface to the less positive (more negative) intracellular surface. This changes the membrane potential near the receptor, which can then activate nearby voltage gated ion channels to propagate the change in membrane potential throughout the cell…
Cells represent the most basic biological units of all organisms, whether it be simple, single-celled organisms like bacteria, or large, multicellular organisms like elephants and giant redwood trees. In the mid 19th century, the Cell Theory was proposed to define a cell, which states:
Every living organism is made up of one or more cells.
Cell motility and migration play important roles in both normal biology and in disease. On one hand, migration allows cells to generate complex tissues and organs during development, but on the other hand, the same mechanisms are used by tumor cells to move and spread in a process known as cancer metastasis. One of the primary cellular machineries that make cell movement…
Organisms harvest energy from food, but this energy cannot be directly used by cells. Cells convert the energy stored in nutrients into a more usable form: adenosine triphosphate (ATP).
ATP stores energy in chemical bonds that can be quickly released when needed. Cells produce energy in the form of ATP through the process of cellular respiration. Although much of the energy from cellular respiration is released as heat, some of it is used to make ATP. During cellular respiration, several oxidation-reduction (redox) reactions transfer electrons from organic molecules to other molecules. Here, oxidation refers to electron loss and reduction to electron gain. The electron carriers NAD+ and FAD—and their reduced forms, NADH and FADH2, respectively—are essential for several steps of cellular respiration. Some prokaryotes use anaerobic respiration, which does not require oxygen. Most organisms use aerobic (oxygen-requiring) respiration, which produces much more ATP. Aerobic respiration generates ATP by breaking down glucose and oxygen into carbon dioxide and water. Both aerobic and anaerobic respiration begin with glycolysis, which does not require oxygen. Glycolysis breaks down glucose into pyruvate, yielding ATP. In the absence of oxygen, pyruvate ferments, producing NAD+ for continued glycoly…
Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects. Cell membrane receptors have three portions: an external ligand-binding domain, a transmembrane domain, and an internal domain. There are three categories of cell membrane receptors based on the consistency of the structure and function of these domains within each category. One category is ligand-gated ion channels which, when bound to a ligand, undergo a conformational change, allowing ions through a channel formed by the transmembrane portion of the receptor. A second category is G-proteins-coupled receptors which have a distinct structure with seven transmembrane domains. Binding of the external domain to a ligand causes the alpha subunit, one of three subunits attached to the internal portion of the receptor, to disassociate from the receptor and create a cellular response. The third category of receptors, the enzyme-linked receptor—also called catalytic receptor…
1Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, 2Muscle Biology Research Group, University of Missouri-Kansas City, 3Pharmacology division, College of Pharmacy, DHLRI, Ohio State University
1Department of Mechanical and Aerospace Engineering, Sapienza University of Rome, 2Institute Pasteur Cenci-Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, 3Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia
The Neuromuscular Junction: Measuring Synapse Size, Fragmentation and Changes in Synaptic Protein Density Using Confocal Fluorescence Microscopy
1Physiology and Bosch Institute, University of Sydney, 2Motor Neuron Disease Research Group, Australian School of Advanced Medicine, Macquarie University, 3Advanced Microscopy Facility, Bosch Institute, University of Sydney
Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation
1Department of Neurology, New York University School of Medicine, 2Department of Health Sciences and Research, Medical University of South Carolina, 3Department of Physical Therapy, University of Nevada Las Vegas, 4Department of Health Professions, Medical University of South Carolina, 5Ralph H. Johnson VA Medical Center, 6Department of Psychiatry, Medical University of South Carolina, 7Division of Physical Therapy, Medical University of South Carolina
Creating a Structurally Realistic Finite Element Geometric Model of a Cardiomyocyte to Study the Role of Cellular Architecture in Cardiomyocyte Systems Biology
1Cell Structure and Mechanobiology Group, University of Melbourne, 2Systems Biology Laboratory, Melbourne School of Engineering, University of Melbourne, 3Department of Biomedical Engineering, University of Melbourne, 4School of Mathematics and Statistics, Faculty of Science, University of Melbourne, 5Department of Engineering Science, University of Auckland, 6Advanced Microscopy Facility, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, 7ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, 8School of Medicine, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, 9Living Systems Institute, University of Exeter
Surface Electromyographic Biofeedback as a Rehabilitation Tool for Patients with Global Brachial Plexus Injury Receiving Bionic Reconstruction
1Clinical Laboratory for Bionic Extremity Reconstruction, Medical University of Vienna, 2Department of Orthopaedics and Trauma Surgery, Medical University of Vienna, 3Department of Bioengineering, Imperial College London, 4Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna
1Clinical Laboratory for Bionic Extremity Reconstruction, Medical University of Vienna, 2Bioengineering Department, Imperial College London, 3Master's Degree Program Health Assisting Engineering, University of Applied Sciences FH Campus Wien, 4Department of Orthopedics and Trauma Surgery, Medical University of Vienna, 5Division of Plastic and Reconstructive Surgery, Department of Surgery, Medical University of Vienna
High Efficiency Differentiation of Human Pluripotent Stem Cells to Cardiomyocytes and Characterization by Flow Cytometry
1Department of Biochemistry, Medical College of Wisconsin, 2Stanford Cardiovascular Institute, Stanford University School of Medicine, 3Department of Anesthesiology, Medical College of Wisconsin, 4Stem Cell and Regenerative Medicine Consortium, LKS Faculty of Medicine, Hong Kong University, 5Division of Cardiology, Johns Hopkins University School of Medicine, 6Cardiovascular Research Center, Biotechnology and Bioengineering Center, Medical College of Wisconsin
An In Vitro Preparation for Eliciting and Recording Feeding Motor Programs with Physiological Movements in Aplysia californica
Immobilization of Live Caenorhabditis elegans Individuals Using an Ultra-thin Polydimethylsiloxane Microfluidic Chip with Water Retention
A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy
1Department of Neurology, Harvard Medical School, 2Department of Neurology, Beth Israel Deaconess Medical Center, 3Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, 4Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 5Department of Neurology, Massachusetts General Hospital
1Sensory Motor Performance Program, Rehabilitation Institute of Chicago, 2Department of Kinesiology and Nutrition, University of Illinois at Chicago, 3Department of Physical Therapy, University of Illinois at Chicago
Applications of Spatio-temporal Mapping and Particle Analysis Techniques to Quantify Intracellular Ca2+ Signaling In Situ
1Institute for Clinical Neurobiology, University of Wuerzburg, 2Department of Synapses - Circuits - Plasticity, Max Planck Institute of Neurobiology, Martinsried, 3Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians University of Munich
Assessing Collagen and Elastin Pressure-dependent Microarchitectures in Live, Human Resistance Arteries by Label-free Fluorescence Microscopy
1Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, 2Department of Biochemistry and Molecular Biology, University of Southern Denmark, 3Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital