Nerves and Muscle 1 - Week 4 Flashcards
What are neurons?
-Neurons are collectors and integrators of information that receive exciting and dampening impulses on their dendrites and the cell body, the perikaryon.
- They integrate the information provided by the impulses on their axon hillock, the portion of the cell
body from which the axon arises.
-If the integration is positive, they send out signals through the axon to other nerve cells or target cells such as a muscle fibre.
-Impulses travel along axons as action potentials.
What are synapses/ glial cells?
-A single neurone can integrate the inputs of hundreds of synapses from many different neurons.
-Much of a neuron’s body and
its dendrites are covered by synapses.
-The spaces not covered by synapses are covered by glial cells.
-Neurons are fully
covered by glial cells or synapses, from the tips of their dendrites to the synapse(s) of their axons, advantageous for tight control of the ionic composition of the thin layer of liquid around them, which is essential for the precise control of action potential generation.
-There is no neuronal
surface exposed to extracellular matrix fluid.”
What are myelin sheaths?
-Myelin sheaths are insulators.
-They are formed by tightly spiralled, very thin layers of Schwann cells, or oligodendrocytes in
the CNS, around the axon.
-Schwann cells are the principle glial (helper) cell of the peripheral nervous system.
-On electron micrographs, it isn’t possible to distinguish between axons and dendrites.
-The myelin sheath appears as dark electron dense band at low magnification and individual dark lines at high magnification.
-When look at myelin layers in high magnification, can see it has intraperiod lines which is equivalent to the extracellular space - likely it represents the glycocalyx on the outside of the cell membrane.
What are Ranvier nodes?
- In myelinated nerves, depolarisation only happens at Ranvier nodes, the areas not covered by myelin.
- These areas are not completely naked, however, but covered by thin outgrowths of Schwann cells.
What is common to all neurons?
-Neurons come in different shapes but what is common to all of them is a very large surface to volume ratio due to extensive branching.
What are key forms of neurons in the PNS?
Pseudo-unipolar or sensory neurones, and motor neurones.
What is the CNS?
-The central nervous system consists of the brain and spinal cord.
-It is encased by a minimally permeable, multi-layered
connective tissue sheet, the meninges which lies inside a casing of bone (skull and vertebral system).
-The fluid inside the meninges is called cerebrospinal fluid.
-It has a different composition to interstitial fluid in the rest of the body.
-The CNS contains the nerve cell bodies of the voluntary nervous system.
What is the PNS?
- Peripheral nerves are covered by ganglia (Schwann cells and satellite cells), which are surrounded by specialised connective tissue cells.
- Less controlled environment.
- The PNS contains the axons and dendrites travelling through rest of the body.
What is white and gray matter?
-When describing the structure of the CNS, the terms ‘white’ and ‘gray’ matter were used.
-Gray matter refers to areas that have clusters of neurones.
-White matters are areas with predominantly nerve connections, which are to a significant percentage
myelinised, which renders them very light due to the high fatty acid content of myelin.
What is an anatomical nerve?
- A collection of axons (of motor neurons) and/ or dendrites (of sensory neurons), bundled and ensheathed into fascicles, which themselves are held together by connective tissue to a nerve trunk.
- Small nerves are just one fascicle, also called nerve fibre bundles.
- Large nerves have several fascicles, held together by a ring of dense collagenous connective tissue (epineurium).
What is the epineurium?
- Collagenous connective tissue surrounding a peripheral nerve.
- Surrounds multiple nerve fasciciles.
What is the perineurium?
- Sheath with flat cells of epithelial character (brownish, tight junctions) with collagen fibres between them.
- Bundles axons into fascicle and forms a seal.
- The perineurium forms a seal around the nerve fibre bundle.”
What is the endoneurium?
- Appears as loose connective tissue (red) between axons/ dendrites within a fascicle.
- Its cells are specially adapted for helping maintain the fascicle.
How do you differentiate between blood vessels and small nerves?
- Larger blood vessels have coagulated red blood cells in them and often a thick outline.
- Nerves have ‘wavy’ content with elongated nuclei when cut obliquely or longitudinally, and often reddish rings with whitish content when cross sectioned.
- They normally have a defined, thin outline (perineurium).
What is the dorsal root ganglion?
A cluster of sensory neuron cell bodies in the dorsal root of a spinal nerve.
How do satellite cells appear?
- As cross sectioned, flat nuclei covering the sensory nerve cell bodies.
- They are the support cells in the PNS ganglia.
What is a summary of the PNS?
- The principle glial cell is the Schwann cell, which produces one myelin sheet per cell or encases unmyelinated nerve
extensions. - Anatomical nerves are bundles of nerve extensions held together by epineurium, perineurium and endoneurium.
- Nerve cell bodies situated in PNS ganglia are covered by satellite cells, the principle support cells of such ganglia.”
What is the membrane potential?
-In the region very close to the outside of the cell, there is an excess of positive ions, and on inside of cell, there’s an excess
of negative ions.
-This balance between the two creates the membrane potential.
-This is just the effect right at the surface of the cell, within the cell it’s a very different environment.
-Charge distribution across a membrane represents a
microenvironment, but one that has a big influence on cellular activity and function.
What is resting membrane potential in a red blood cell?
-30mV.
What is resting membrane potential in smooth muscle?
-90mV.
What is resting membrane potential in a neurone?
-70mV.
How many Na+ and K+ ions do the pump move in and out?
Kicks out 3 sodium ions for every two potassium ions that enter.
What happens once the threshold potential is reached?
-Once it gets to the threshold potential, rapid depolarisation of neuronal cell membrane occurs.
-Stronger the stimuli, the faster
the threshold is reached.
-Characteristics of action potential same for all stimulus.
What is the all or none law?
-The principle that the strength by which a nerve or muscle fibre responds to a stimulus is not dependent on the strength of the stimulus.
- If the stimulus is any strength above threshold, the nerve or muscle fiber will either give a complete response or no
response at all.
What are the features of an action potential?
- There’s a rising phase due to rapid depolarisation, where it goes above 0mV membrane potential such as there’s a positive charge on the inside of the cell membrane.
- Then goes back down below the resting potential and then slowly increases back to resting membrane potential, hyperpolarisation.
- At the peak, there’s an excess of positive charge - it’s a localised effect on the membrane.
What is the ionic basis of action potential generation?
-At the rising phase there is rapid depolarisation that takes membrane potential above 0mV.
-This is due to the opening of
voltage dependent Na+ channels, which are normally closed at resting membrane potential, but once it gets to threshold potential, they open and lots of Na+ influxes.
- At the point where you’re measuring membrane potential, have accumulation
of positive charge on inside of cell membrane.
-Then almost as quickly, have a repolarisation involving the efflux of K+ through voltage dependent potassium ion channels that are normally closed at resting potential.
-Sodium ion influx is reduced because membrane potential is changed.
-Enough K+ will leave from inside to outside of cell membrane such that enough negative charge is restored on the inside of the cell membrane.
What is the fast positive feedback?
-Once get triggering of events, membrane is depolarised and there is increased permeability of Na+, so an increased influx of
Na+.
-This leads to a positive feedback event in the action potential upstroke, taking it from negative to positive membrane voltage on inside of cell.
What is slow negative feedback?
- In the action potential downstroke, as membrane becomes depolarised, there is increased K+ permeability, so increased K+ outflow, leading to membrane hyperpolarisation.
- Inactivation of voltage gated Na+ channels to reduce Na+ influx is not enough for action potential repolarisation, need opening of voltage gated potassium ion channels.
- For action potential to occur, voltage gated sodium ion channels must activate more quickly than voltage gated potassium ion channels, so need a change in Na+ permeability that is more active and rapid than the change in K+ permeability.
What is the refractory period?
-The refractory period is a period of time during which a cell is incapable of repeating an action potential.
-In terms of action potentials, it refers to the amount of time it takes for an excitable membrane to be ready to respond to a second stimulus once it returns to a resting state.
-The depolarisation that produces Na+ channel opening also causes delayed activation of K+ channels and Na+ channel inactivation, leading to repolarisation of the membrane potential as the action potential sweeps along the length of an axon.
-In its wake, the action potential leaves the Na+ channels inactivated and K+
channels activated for a brief time.
-These transitory changes make it harder for the axon to produce subsequent action
potentials during this interval, which is called the refractory period.
-Thus, the refractory period limits the number of action
potentials that a given nerve cell can produce per unit time.
What is the relative refractory period?
- The relative refractory period is the interval of time during which a second action potential can be initiated, but initiation will require a greater stimulus than before.
- Corresponds to hyperpolarisation.
What is the absolute refractory period?
- The absolute refractory period is the interval of time during which a second action potential cannot be initiated, no matter how large a stimulus is repeatedly applied.
- Corresponds to depolarisation and repolarisation.
What is nerve conduction velocity affected by?
Axon diameter, myelination and temperature.
How does axon diameter effect nerve conduction velocity?
- Increasing diameter, increasing nerve conduction velocity.
- Less internal resistance as current travels further before being dissipated.
How does myelination effect nerve conduction velocity?
- Decreases current leakage across membrane over internodal surface.
- Current travels further before being dissipated.
- Voltage gated channels concentrated at nodes of Ranvier.
- Gating of channels only has to occur at nodes, not continuously as in unmyelinated tissue.
What is spatial summation?
Spatial summation occurs when multiple presynaptic neurones together release enough neurotransmitter (e.g. acetylcholine) to exceed the threshold of the postsynaptic neurone.
What is temporal summation?
- Temporal summation occurs when one presynaptic neurone releases neurotransmitter many times over a period of time.
- The total amount of neurotransmitter released may exceed the threshold value of the postsynaptic neurone.
- The higher the frequency of the action potential the more quickly the threshold may be exceeded.
What is the EPSP?
-An excitatory postsynaptic potentials is a temporary depolarisation of postsynaptic membrane caused by the flow of positively charged ions into the postsynaptic cell as a result of opening of ligand-sensitive channels.
-Increasing amounts of
neurotransmitter gives rise to a very short term depolarisation.
-Change in membrane potential is proportional to amount of
neurotransmitter released.
-These are small changes in membrane potential.
-If two nerves fire, and are close physically in terms of both distance and time, get a degree of summation.
How does the EPSP influence
post-synaptic action potential?
-Stimulation from nerve leads to EPSP but it may not reach threshold potential.
-If stimulations are more frequent, that summation gets closer to threshold potential and if interval is shorter, summation ensures each reaches threshold, and then
in the nerve you’ll detect the generation of the action potential which will move all the way down the axon.
What are key properties of fast excitatory synapses?
-They are ionotropic events, so ligand-gated cation selective ion channels.
-Mainly due to Na+ influx into post-synaptic cell which depolarises membrane potential of post-synaptic cell.
-Gated by neurotransmitter molecule, centrally by the amino acid glutamate, glutaminergic, and peripherally by acetylcholine, cholinergic. EPSP brings Vm nearer to threshold, increasing
chance of action potential firing and increasing excitability and summation to elicit action potential.
What is the IPSP?
-An inhibitory postsynaptic potentials (IPSP) is a temporary hyperpolarisation of postsynaptic membrane caused by the flow of negatively charged ions into the postsynaptic cell.
-So for example, have basal K+ channels and ligand gated anionic channel.
-Chloride ions in excess on outside of cell and in lower concentrations inside.
-Release from neurotransmitter of amino acid GABA, an inhibitory neurotransmitter. GABA interacts with specific receptor connected to an ion channel, leading to opening
of that ion channel and movement of chloride ions from outside to inside of cell.
-Membrane potential becomes more negative.
-Release of GABA causes hyperpolarisation.
What are some properties of fast inhibitory synapses?
-It’s an ionotropic event as has ligand gated Cl- or K+ selective ion channels.
-Mainly influx of Cl-, hyperpolarising membrane
potential of post-synaptic cell. IPSP brings Vm further from threshold, decreasing chance of action potential firing, and
summation inhibits action potential firing and reduces excitability.
-Inhibitory neurotransmitters are amino acid molecules.
What is the structure and function of muscles?
-Striated (skeletal/voluntary) muscle attaches to the bones by tendons and appears stripy under a microscope.
-Skeletal muscles contract and relax to move bones at a joint.
-The cells in striated muscle are highly specialised muscle fibres.
-Each fibre contains many nuclei (multinucleate), mitochondria (provides ATP for contraction) and sarcoplasmic reticulum (contains
calcium ions).
-The cell membrane of a muscle fibre is the sarcolemma.
-Parts of the sarcolemma fold inwards across the fibres
and stick into the sarcoplasm (cytoplasm containing organelles such as mitochondria).
-These folds are fibules and help spread electrical impulses through the sarcoplasm.
-Muscle fibres are made of myofibrils, which are made of many short units called sarcomeres.
-The ends of sarcomeres have a Z line and the middle has an M line (attachment for myosin).
-They contain bundles of protein filaments (myofilaments) called actin and myosin which move past each other to make muscles contract.
-They produce alternating patterns of light and dark bands: Dark A bands contain the thick myosin filaments and some overlapping thin actin filaments.
-Light I bands contain thin actin filaments only.
-Around the M line is the H zone which contains myosin filaments only.
-When the muscle contracts, the dark band overlaps the intermediate band, shortening the length of the muscle and the sarcomere.
What is the sliding filament model?
-Sarcomeres contract when myosin interacts with actin to form a cross bridge - this happens in a sequence of steps: An action
potential travels into the muscle fibre via T tubules, which are in contact with the sarcoplasmic reticulum (muscle ER).
-As the action potential reaches the sarcoplasmic reticulum, Ca2+ ion channels open and Ca2+ diffuses into the sarcoplasm.
-The calcium ions released by the sarcoplasmic reticulum now bind to troponin.
-This causes the tropomyosin molecule to move, which exposes the myosin binding site on the actin filament.
-This allows myosin to attach to actin and form the
actin-myosin cross-bridge.
-Once attached to actin, the myosin heads change shape, pulling the actin filaments along which releases a molecule of ADP.
-Then, a molecule of ATP attaches to the myosin head, causing it to change shape and detach from the actin filament.
-After this, ATPases are activated by the Ca2+ ions released by the sarcoplasmic reticulum.
-These ATPases breakdown the ATP attached to the myosin heads - this allows the myosin heads to return to its original position.
-The myosin heads are now detached and can attach to another binding site further down the actin filament and the process repeats.
-This process results in the actin filaments in one sarcomere being pulled in opposite directions, towards each other.
-As filaments slide past one another it causes the sarcomere to shorten - this process is known as Sliding Filament Model.
What is a sarcomere?
-A sarcomere is the basic contractile unit of muscle fibre.
-Each sarcomere is composed of two main protein filaments—actin and myosin—which are the active structures responsible for muscular contraction.
-The thick filaments are myosin and the thin filaments are actin.
-Sarcomeres
are held in register by cross connections at the level of every Z disk and the middle of each sarcomere.
-This generates the striated appearance of skeletal muscles and the heart - that’s why they’re called striated muscles.
What is myosin?
-Myosin is the principle motor protein for movements by interacting with filaments.
-Once it binds tightly to actin filaments, it releases ADP and then it needs to take up ATP in order to come off the actin filament again and initiate a further contraction.
-In order to detach from the actin filament after going through a cross bridge cycle (myosin pulling itself along actin filaments), the myosin head needs to take up a new ATP.
-Once the intracellular ATP has vanished in the striated muscles, normally a
few hours after death, rigor mortis occurs, the stiffening of muscles after death.
-If ATP is used up, the lack of oxygen doesn’t allow it to be replenished in mitochondria, and eventually most myosin heads get stuck as they can’t detach, leading to stiff
muscles.
What are actin filaments created from?
Individual actin molecules.
What is the structure of a muscle fibre?
-Several hundred myofibrils are tightly packed in a muscle fibre.
-A muscle fibre is a synctyium, hundreds of precursor cells
have fused to form a fibre which can accommodate many and long myofibrils.
-Each muscle fibre is about 20-100micrometres
thick, and 1mm to 8cm in length.
What is the length-tension relationship?
-The amount of force developed by a sarcomere depends on the degree of overlap between thick and thin filaments.
-Thus the force a muscle can develop is dependent on its starting length.
-At full stretch, few of the myosin heads have access to actin in the thin filament and the force is weak, at optimal length, all of the myosin filaments have access to actin, the force is maximal,
at full contraction, then ends of the thin filament get in each others way and the force is reduced.
-Our muscles are adapted to
be in the maximal range of their length-tension relationship for our most frequent daily movement.
What is endomysium?
-Loose connective tissue with some delicate and some strong fibres, surrounding each muscle fibre.
-Connects to basement
membrane.
What is perimysium?
-Mixed connective tissue, some dense, some loose, separating groups of muscle fibres into fascicles.
-Main venue for nerves
and supporting blood vessels.
What is a fascicle?
Bundle of muscle fibres held together by perimysia.
What is epimysium?
Relatively loose connective tissue between fascia and muscle body.
What is fascia?
Dense layer of connective tissue covering the muscle.
How do striations arise?
The striations arise because the myofibrils are held in register by intermediate filaments (consisting primarily of desmin) that
link neighbouring Z discs laterally as well as longitudinally.
What does the non-myofibrillar
cytoskeleton provide?
-At the level of each Z-disc, the non-myofibrillar cytoskeleton (desmin fibres) provides a strong link to the basement membrane
and into the surrounding connective tissue.
-Force is not just transmitted longitudinally, it is also dissipated laterally, into the
collagenous tissue network surrounding each fibre.
What is muscular tissue?
-Derived from mesoderm and composed of cells, or multinucleated syncytia, whose cytoplasm contains filaments made of contractile proteins, primarily actin and myosin.
-Skeletal muscle, due to the organisation of those proteins, takes on a striated appearance.
-The proteins are arranged in a way to allow for the maximum generation of force in that direction.
-Cardiac muscle is different from skeletal muscle as the striations are less obvious, but it’s still striated.
-For smooth muscle, don’t see
striations.
How is smooth muscle structurally organised?
- For skeletal, striations indicate very clear organisation of contractile proteins.
- By contrast, the way in which proteins are arranged in smooth muscle is more net like in terms of structure.
- This allows for a change in shape of the particular organ in which you’ve got smooth muscle, whether it’s the GI tract or the bladder, for example.
- Smooth muscle is supported by and contains connective tissue.
- Unlike skeletal, smooth muscle doesn’t act upon structures such as bones, there isn’t a tendon that links the muscle to a fixed part of the body.
- If consider stomach, it’s not fixed within abdomen in way skeletal muscle would be fixed to bones, but within stomach will see variety of different types of smooth muscle which perform different roles.
