FSF Module V (Muscle and Nerve Tissue)

Whta is CNS and PNS

CNS- brain, spinal chord

PNS- peripheral nerves, associated ganglia, connections to CNS

What is th classification fo muscle types?

Label this neuron:

What are the two nerve cell types?

Neurons: large, functional unit responsible for electrical impulses

Supporting cells (nueroglia): support, nurture/protect neurons central+peripheral neuroglia

In the top image identify which are the nueroglia and axons (white matter) and which are the nueron nuclei (gray matter) in the spinal chord

The inner (darker region) gray matter (PNS and CNS) of the spinal chord has the neuron nuclei while the white matter (paler) outside contains the neuron axons and nueroglia

What are th different types of neurons?

Sensory neurons: receive infor and conduct impulses to CNS for processing and analysis

Interneurons: conduct info and connect neurons (specifically sensory to motor and vice versa) (most abundant type we have)

Motor nuerons: transmit info from CNS to motor cells/effector cells to extert response (muscle/glands)

What are the different neurons?

• pseudounipolar neurons: single process that extends from cell body branching into peripheral process and central process (not veyr abundant found mainly in spinala dn ganglia)

• Bipolar: single axona dn dendrite, not veyr abudant found in sensory organs

• Multipolar: usual model of neuronwith many dendrites, single axon, most abundat type.

Describe the components of the nueral soma.

Nucleus: has euchromatin (pale uncondense)

Nissl bodies: granular structures with polyribosomes and RER, stain basophilic (purple)

Lysosomes

Mitochodnria

Golgi

Inclusions

• Lipofuscin-containing granules: formed by residual bodies of lysosome (incres in number with age)

• Lipid droplets (occasionallly present)

• Melanin-contsining droplets

Cytoskeleton

• nuerofilament (10nm)

• Microtubules (24nm)

• Microfilaments (6nm)

Describe neuronic dendrites

Recieve stimuli from senosry cells, converting them into electrical impulses transmitted to soma (not action potnetials yet). Branches contain different spine swhich increase area availbale for synapse transmission (decrease with poor age+nutrition) ***has many mitochondria

Dscribe axon structure:

Axon hillock, no nissl bodies, lots of microtubules and nuerofilaments wth mitochondria and vesicles (here elctrical pulse generated)

Axon, has surroudning plasmam membrane( axolemma), cytoplasm alled axoplasm, no RER or golgi, lots of cytoselton and SER and elongated mitochondria. Protected in generalby glial cels because it is thin and more fragile+ can be up to 1m long

Axona transport systems

• anterograde trasnport: cell bodyto axon terminals, regenration of vesicles and proteins, MAPs like kinesin play important role in this

• Retrograde transport: axon terminal to body, recycling r materials, Dyenin plays important role in this.

Recognize neurons under microscope:

What are Astrocytes with reference to neurons?

• Largest of neurglial cells

• Blood brain barrier: Surround blood vessel thru extended pedicles (vascular feet) reinforcing the blood-brain barrier to regulate exchange +passage from blood to brain stoma. Formed by tight junctions between adjacent endothelial cells, astrocytes reinforce these junctions by connecting trhu anchoring junctions

• Surround neurons, taking ions after having compelted their function+suplying energy fr metabolism

• In contat w/ meninges (pia mater), protective barrier between pia mater and nervous tissue

• In brain, astrocytes form scar tissue (glial scar) after injury to CNS

Can be protoplasmic:

• gray matter, short processes, intermediate filaments, mainly form blood brain barrier

Fibrous:

• white matter, long slder processes, many intermediate filaments

What are oligodendrocytes with reference to nuerons?

Protect axons of neurons found in white and gray matter, have small condense nucleus and short process… surround axon and create concentric layers of myelin, aiding in eletrical trnamission speeds, each oligodendrocyte can myelinate several axons at once.

What are microglial cells with reference to neurons

Similar to astocyte sudner microscoep, phagocytic cells. Arborized, immune cells of CNS.. when activated they change shape, becoming liek macrophages and secreting cytokines to recruit other immune T cells (act as APCs (antigen presenting cells)

What are ependymal cells with reference to neurons

Derived form nueroepithelium, line nueral tube and brain ventricles, some contain cilia (move cerebrospinal fluid), some contribute to formation of choroids plexus (tissue that lines ventricles of brain in innermost meninges (pia mater)

What are Schawnn cells with reference to nuerons

Similar to oligodendrocytes, protecting and isolating neurons but doing so in the PNS. Oligodendrocytes are flat cells (with basement membrane), few mitochondria and small golgi region.. form myelinated covers and unmyelinated covers (schawnn cells just surround axons)-single schwann cell can only insulte a single axon

What are the three types of synapses?

1. Axodendritic synapses: axon dendrite

2. Axosomatic: axon soma

3. Axoaxonic: between 2 axons (much less common)

Electrical synapses can be bidirectional (faster)while electrical are more common and unidirectional

This is synaptic cleft under microscope:

What is a neuromuscular junction?

A type of synapse in which an axon innervates muscle (called motor unit), with the motor end plate connected to the muscle which is where the different synapses take place, we can see that they branch into sveveral axon terminals. The motor end plates in the postsynaptic membrane have junctional folds which are deep invaginations of the muscle of ell plasma membrane (sarcolemma) whihc increase surface area for the neruotransmitter (ACh) to interact

How does myelin sheath get formed?

Keep this image in mind and know how to identify:

What are Schmidt-Lanterman clefts?

Incisions in myelin know as shcmidt-lantermn clefts that allow for communication between innner and outer cytoplasm to take place.

Whata re the nodes of ranvier?

In PNS: node is covered by interdigitated cytoplasmic processes of adjacent schawnn cells protecting axon

In CNS: myelin free surface covered by a foot plate of astrocytes, protecting unmyealinated regions.

Internodes is the space between node of ranvier

Explain structure of the nerves

They are cordlike bundles made of nerve fibers surrounded by connective tissues, seen in microscopy as white is myelin surrounding the nerves. Conatins the following:

• Epinerium: Outermost, consisting of dense fibrous connective tissues, often embedded in adipose tissue

• Perinerium: surroduns each bundle of nerve fibers, made up of speacialized connective tissues which block+regulate trhu tight junctions (form blood-nerve barier)

• Endoneurium: surrunds each individual nerve fiber, made of reticular fibers and collagen, containign some fibroblasts.

The nerves are axons+supporting cells and the gnaglia is the neuronal bodies

In the spinal cord and cerebellum where is the white or grey matter?

What are ganglia?

Encapsulated aggregations of neuronal cell bdies (soma) outside the CNS+ abundant small glial cells (satellite cells) surroudning them

The nerves are axons+supporting cells and the gnaglia is the neuronal bodies

What are the meninges?

Membranous coverings of brain and spinal cord, formed by connective tissue, protecting inner nerve tissue. 3 layres

• Dura Mater: outermost, lines bony skull and close to vertebrae

• Arachnoid Mater: intermediate, abutting the dura

• Pia Mater: innermost, high vascular, directly on brain surfaceand spinal cord.

Explain the organization of connective tissue in muscles

• Epimysium: surrounds entire muscle and forms a connecion between skelatl muscle and other muscles and tendons, which also connect to bones,.

• Perimysium: connective tissue around each muscle bundle

• Endomysium: surrounds each individual muscle cell

Label these images of skeletal muscle.. and what are skeletal muscle cell characteristics?

• multinucleated, on periphery

• Long large cells

• Basement membrane known as sarcolemma, forms deep invagination known as T-tubules. T-tubules together with terminal cisternae (end of sarcoplasmic reticulum) to form triads. Cytoplasm known as sarcoplasm.

• Striations which corresponds to myofibrils and thin filaments

• 3 different cell types ahve different metabolic compnents, shown by differences in staining:

  • Red fibers type I: abudnant in myogobin, slow contraction, abundant mitochondria, strong oxidative capcity, more vascularized, thinner less fibers

  • White fibers (type Ilb): fast contraction but fatigue easily, low myogobin, few mitochondria, fast anaerobic glycolysis metabolism, larger and more myofibrils, less vascularized,

  • Intermediate fibers (type Ila)

What are the different skeletal muscle type fibers?

You can change between type B to A during resistance training but not between types I and II

When you do force training, you generate more myofibrils in parallel, the dimaete of the muscle fibers increases, having more force but not as much velocity.

How to myofibril growths in skeletal muscle affect strength and velocity?

• growth in parallel increases strength

• Growth in length increases velocity

Identify strcutures in the image

Explain sarcomere structure

Components:

• Myosin akes up the thick fillaments in the center

• Actin makes up thin filaments attached to Z lines (made up of alpha actinin)

• Tropomyosin is on the actin binding sites

• Tropnin binds to calcium and reveals active sites of actin (TnT binds troponin complex to tropomyosin, TnI binds to actin and troponin T, TnC binds calcium)

• Desmin located at Z disc, binds Z disc to plasma membrane tro transmit contraction of th cell.

• Dystrophin: binds actin to cel membrane

• Tropomodulin and nebulin are other proteins that help stabilization

• M line proteins (myomesin, M-protein, obscurin)

• Protein C

• Titin: stabilization of thick filaments

Bands:

• A band: thin and thick filaments overlap, seen as a dark band. (Actin and myosin)

• I band: only thin filaments (actin), seen as light

• Z disc:

• H bands:inmiddle of A band, bare region of thick filaments, only myosin tails (seen as light)

• M lines: dark lines in middle of H zone, corresponding to croos sections between thick filaments

Label this diagram of the sarcomere:

Describe skeletal muscle regeneration

Progenitor cells- satellite cells repair muscle cells int he case of muscle degradation, they become activated under the influence of myogenic regulatory factors and become myoblasts finally differentiating into mature muscle cells.

What are DHP and RYR and SERCA proteins

Allows Ca2+ transmisison

4 DHPR molecules on T tubule changes confromation upon stimulation and act on one RYR, which opens by changing conformation to allow Ca2+ release from cells.

SERCA ats as a calcium pump to pump Ca2+ into the reticulum.

THIS COUPLING ONLY OCCURS IN SKELETAL MUSCLE

Describe cardiac muscle features

• Striated

• Self excitatory

• Electrically coupled

• Nuclei centrally located, multinucleated

• Intercalated discs separate the cells and are seen as darker lines.

• Striations are more difficult to see (weaker)

• Have darker fibrolasts in endomesyum

• Abudant mitochondria

• Have diads instead of triads- sarcoplasmic reitculum and t tubules at z lines

What are cardiac muscle intercalated discs?

They are interidgitated cytoplasmic expansions responsibe for mechanically and electrically coupling heart cells, they are aligned with Z discs, runing transversally (have zonula adehrens and desmosomes- mechanical coupling) and laterally (gap juntcion that transmit electrical signals thru ion transport- electrical coupling)

How is cardiac muscle contraction? In comparison to skeletal muscle?

• same.. dependant on Ca2+

• Different.. contraction starts thru purkinje fibers and cardiac myocytes- transmitted to mucsle cell thru GAP junctions via electrical coupling (ion trnasport)… calcium enters cell trhu t tubule, tansported to cytoplasm and triggers release of intracellular calcium from SER.

What are smooth muscle chracteristics?

• no striations (fusiform)

• Each fiber formed by a single cell kkept together by connective tissue and connect thru GAP junctions OR single individual cells innervated each by a separate nerve fiber

• surrounded by a basal membrane like endomysium

• No t tubules or sarcoplasmic reitculum, insted have pinocytic caveolae and SER in periphery

• For non voluntary contraction

• modulated by innervation and chemical stimuli,

• Slower contraction than skeletal muscle

• Organization:

  • Elongated central nuclei-not to be confsd with those f connective tissue or more heterochromatic and flatter fibroblasts— smooth muscle cells are more euchromatic

  • Circular layer than runs tranvesally and around and a longitudinal layer that runs along the tube

Instead of sarcomeres what can be found in smooth muscle?

contractile fiber

Thin filaments:

• actin

• Tropomyosin

• Caldesmon and calponin (actin binding porteins instead of troponin)

Thick filaments:

• smooth musle myosin (no need for troponin to cover active sites since it has low actin affinity)

• Side polar orientation— no H zone of central line (look at image)

Dense bodies are membrane associated and act as sort of Z lines to transmit the contraction to the rest of the cell.

• Intermediate filaments to stabalize and transmit: Desmin +Vimetin

• Alpha actinin

• Other adhesion proteins

Describe smooth muscle contraction

• also Ca2+ dependent

• Slower than skeletal muscle contraction no motor end plate, innervation occurs at a distance, therefore instead of synapse regions there are varicosities

• Two types of innervation:

  • Visceral: very few nerve endings, connected thru gap junctions-electrically coupled-rythmic contraction

  • Multiunti contraction: few gap junctions, every cell individually innervated-more rapid/precise control contractions.

What is the coupling mechanism in smooth muscle cells?

• calcium activates an MLCK (myosin light chain kinase), whihc phsophrylates the light chain of myosin- increasinf the affinity of myosin for actin—casues contraction

• Since in smooth muscle the binding site is always exposed, the continouos phosphorylation of myosin causes the myosin to bidn to the actin and contract

• At the same time there is. Posphatase dephosphorylating myosin to remove its affinity

How does msooth muscle relax?

Explain the different patterns of smooth muscle contraction

Because the smooht mscle has so many different mechanism by which to contract, the different mechanism causes different pattenrs

How are long lasting contractions created in smooth muscles?

Neessary for long periods of time— like sphincter (23hrs a day)

• since we can control intracellular calcium levels, we can sustain contraction for a long time by keeping intermediate levels of calcium to increase some of the portions of myosin’s affinity for actin

• An initial high peak is necessary but after thisit can eb maintained at interediate levels, meaning it does things slower but with alow level of contraction and no excessive energy consumption.

How do the three diff. Muscle types regenrate and growth?

Skeletal:

• Increases in size by depostiing collagen (called hypertrophy)

• Regenrate thru satellite cells as muscle cell themsleves cannot divide

• Restricted

Smooth:

• hypertrophy

• Cells can divide and proliferate

• Mesenchymal cells that differentiate into them (vascular pericytes)

• Extensive

Cardiac muscle:

• hypertrophy

• Circulating progenitor cells that differentiate into them and resident stem cells

• Poor

Muscle types summary:

What’s the difference between chemica and eletrical synapses?

Chemical: (in uman body most are like this so we mostly talk abt this)

• some delay

• NEurotransmitters to excite or inhibit

• Unidirectional

• Large synaptic cleft

• Not necessarly linked to ion channels

Electrical

• no delay

• Ions

• Noinfo changes

• Bidirectional

• Open chhanel between cells

• Minimal intercellular space

Describe the neuromuscular synapse:

1. Presynaptic bouton:

• Sodium potassium volateg gated channels for action potential transmission

• Calcium voltage gated channels for muscle contraction— accumulaed calcium exits thru an Na/Ca countertransport pump, one calcium leaves while three Na enter— uses ATP

• Neurotransmitter vesicles(ach)

1. Synaptic cleft

• neurotransmitters diffuse trhu cleft an reach postsynaptic muscle fiber

• Ach esterase in the cleft breaks down Acetyl choline in the cleft

1. End plate

• hyperdense folds increase surface area, where Ach receptors are located

• These nicotinic receptors and ligand-agted and open when two Ach moelcules bind— trigger Na+ influx an local depolarization leading to Na+ volatge gated channels opening- propagate actino ptential

• No potassium volatge gated channels as safety mechanism— need a lot of Ach to transmit depolarisation

1. Sarcollema

• specialized membrane surrounding striated muscle fiber with invaginations (more surface area)

• Here at teh end plate, no sodium volatge gated channels, hence it propgates electronically not chemically, therefore the amplitude decrease and action potentia will beingin neraby area where those channels can be found (must be -60mV for action potential to take place)

How is Ach stored in vesicles? And releaseD?

Proton pump (ATPase) to maintain low pH, simultaenouesly there is an Ach/proton counter transport- so Ach enters

Vesicle fusion with memebrane and Ach release is mediated by SNARE proteins (Solule NSF attachment Protein receptors).

• calcium contacts with synaptotagmin

• Synaptobrevin in neurol membrane conacts other proteins which will contact and push vesicles to membrane, causing them to fuse

• Also works w/ lysosomes-membrane fusions

• Can works in two ways:

  • Classical: fully integrated due to clathrin

  • Kiss and Run: no full fusion, release thru fusion pore.

Explain the two main types of postsynaptic receptors

Ionitropic receptors: direct effect, membrane bound that respond to ligand binding by opeening ion channel

Metabotropic receptors: indirect effect, neurotransmitter binds to G-couple receptors, cause secondary messengers to effect— to open ion channels (in same or other parts- unlike ionitropic receptors which is only local) and/ protein synthesis, transciption etc

Explain Excitatory vs inhibatory post synaptic potentials

Excitatory(EPSPs):

• electronic propagation- decreases w/ distance

• propgates homogenusly in all directions

• Begins in trigger zone (requires -60 mV)

• Use ionotropic and metabotrpic receptors

• Retrograde proagation of action potential: goes to soma but can retrograde back into dendrites (since it propagates equally in all directions)- causes neural plasticity via calcium channels

Inhibitory(IPSPs) (redce/block action potnetial firing probability)

• ions with equilibrium potential more negative than resting potential are inibitory

  • Cl- channels: increase Cl- conductance, ECl is 90mV

  • K+ channels: increase K+ conductance, EK is -95mV

• Generated by different receptors

  • Glycine (tetanus) and GABA via Cl- inhibits ionotropic receptors

  • 5HY2C via IP3/DAG, 5HTA1 via decrease in cAMP, and muscarinic recptor M2 via decrease in cAMP and opening f K+ channels inhibit Metabotropic receptors

• Take place near trigger zones

• Originate in soma to compensate for the fact that excitatory potentials are more abundant and have a higher amplitude

Explain presynaptic inhibition and facilitation

Inhibition:

1. Small sustained depolarization (ex: enkephalin- as painkiller)

   1. Blocks Nachannels so decrease axonal action potential

   2. Less volatge gate Ca channels opened

   3. NT (neurotransmitter) release reduced

2. Hyperpolarization

   1. GABA acts on neurons via GABA ceptors to Lower the aperture of C2+volateg gated channels, hence less NT release.

3. Ca2+ voltage gated chanels blockage

   1. Less Ca entering, less NT release (opiods do this)

4. Non-Ca mediated Neurtrnamsitter exocytosis block

Facilitation: Potentiate NT release— serotonin does this

Keep this in mind:

What are the three different synapses?

For exam keep in mind:

The calcium from the reticulum is important only, Ca2+ from blood activate K+ channels for membrane potential, hence it is harder to start (regulator) — hypoglycemia causes muscle contraction

For example see

Ok