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neuron vs neuroglia???
- NEURON: functional cell of nervous system; no division
- communication to muscles or glands, etc.
- produce action potentials!!!
- no division... so once it's damage, it can't really be repaired, cannot be regenerated and can loose function
- NEUROGLIA: "support cells"; may divide
- repair, regulate, protect, and support
- outnumber neurons ~20:1!!! but don't produce action potentials!!!
- may divide... need to repair and regulate during infection or trauma
what are the CNS neuroglia (4) vs PNS neuroglia (2)???
- CNS glial cells: astrocytes, microglia, ependymal cells and oligodendrocytes
- PNS glial cells: schwann cells and satellite cells
1st CNS neuroglia: ASTROCYTES
... general features? (6)
- 1. largest and most numerous CNS neuroglia
- - structural framework/support for CNS (very abundant and have an extensive cytoskeleton, they have their own internal cytoskeleton)
- 2. maintain extracellular environment
- - regulate osmolarity of K+, Na+ and CO2 (basically of ions and gases)
- - conduit for nutrients, ions and dissolved gas from vasculature to/from neurons
- - 1 process is wrapped around both the axon and the capillary! acts like a channel from nutrients from blood to neurons w/c is great cause neurons need lots of ions and gases
- - communicate with each other and neurons via gap junctions
- 3. enhance or supress synaptic communication by absorbing and recycling neurotransmitters (especially glutamate and GABA)
- - shows how it has hands on everything
- - since involved with synapse, can absorb NTs released
- - impt bec the key to neuronal transmission is to be fast and to react, can't reverse signal until NTs are absorbed, NTs shouldn't be hanging around because signal gone
- - figure shows an astrocyte surrounding a SYNAPSE... unmyelinated regions on NODES, astrocyte surrounds these nodes
4. contribute to neuronal development in utero
- 5. components of the blood brain barrier.... feet of astrocytes cover capillaries!!!
- - limits movement in & out... also limits blood flow and volume via chemicals secreted by astrocytes
- 6. stabilize damaged neuronal tissue
- - migrates to damaged area to wall of injured tissue and stabilize area
- - astrocytes allow more blood to enter damage site to bring in cells needed for repair
- - can move to site of damage so if you have a trauma, it tries to stop it from spreading
- - brain is like butter... astrocytes bring structure to something to prevent damage
2nd CNS neuroglia: MICROGLIA
... general features?
- 1. wandering police force and janitors
- - phagocytose debris & pathogens
- - monitor and patrol the brain for infection
- 2. monocyte/macrophage lineage: enter CNS during embryogenesis
- - originally an immune cell, makes their way to the brain during development
- - can upregulate and increase in concentration in times of need
3rd CNS neuroglia: EPENDYMAL CELLS
... general features?
- - line the brain ventricles and central canal of spinal cord
- - produce, circulate (through cilia in ependymal cells) & monitor composition of CSF
- - cushions the brain
- - transports dissolved nutrients, gases and waste
4th CNS neuroglia: OLIGODENDROCYTES
... general features?
- - only in CNS!!! for PNS = schwann cells
- - produce myelin for CNS neuron to insulate them
- - it insulates neuron to prevent ion loss is neuron, important to neuronal communication
- - myelin = layers of oligodendryte cell membrane (shown)
- - concentric layers of oligodendrocytes cell membrane wraps around axon (shown above)
- - many oligodendrocytes contribute to myelination of 1 axon
- - 1 oligodendrocyte can wrap around several axons
- - but 1 oligodendrocyte can't myelinate a whole axon so needs several oligodendrocytes to myelinate a whole axon
unmyelinated region; "spaces"; term used in both CNS and PNS
node of ranvier
single myelinated region
acts as insulation around axon; limits leakage of ions out of and into the axon; therefore, increasing conduction of electrical signals; usually found where speed is vital ex. cortex of spinal cord (reflexes) and peripheral nerves; made of lipids (gives brain its white color!!!)
white matter vs grey matter
- white matter: are regions of CNS & PNS containing numerous myelinated axons; myelin = lipid = fat; so the fat gives it the white color
- grey matter: regions of CNS & PNS contains neuronal cell bodies, dendrite, and unmyelinated axons ; has clusters of rough ER and ribosomes called NISSL BODIES that give grey matter its grey color
- SUMMARY: white = myelinated = bec of fat in myelin
- SUMMARY: grey = unmyelinated = bec of nissl bodies
notice a FLIP: grey matter on periphery of CNS but white matter on periphery of PNS
how is the PNS neuroglia different from the CNS neuroglia?
- PNS are all the neuronal tissue outside the brain and spinal cord
- delivers sensory info to CNS & carries out motor commands
- PNS is not protected by blood brain barrier, blood-CSF barrier or cranium SO...
- it's more readily exposed to toxins and mechanical trauma (more vulnerable than CNS)
- so the entire neuron is protected or covered by neuroglia
- in PNS, the neurons are engulfed by neuroglia bec not as protected as CNS
1st PNS neuroglia: SATELLITE CELLS
... general features?
- protects ganglia (neuronal cell bodies in PNS) from surrounding environment (from the ECF) which might not be always perfect
- regulates gases, nutrients and NT surrounding ganglia
- similar to astrocyte in CNS!!!
2nd PNS neuroglia: SCHWANN CELLS... general features?
- produce myelin for PNS axons
- a schwann cell can only cover one axon (diff from oligodendrocytes!!!)
- axons are covered by multiple schwann cells
- unmyelinated axons are also covered by schwann cells... they enclose the axons and not myelinate them... don't make concentric layers of cell membrane of schwann cell... to protect from ECF
- similar to oligodendrocytes in CNS
unmyelinated PNS axon vs myelinated PNS axon?
- unmyelinated: has one coat of myelin... schwann cell spreads a thin layer of myelin to surround axon in 1 loop not to insulate it but to protect it from ECF
- myelinated: has mutiple coats of myelin... schwann cell spreads layers of myelin for insulation
demyelination disorder: primary damage vs secondary damage???
- primary damage: myelin and/or myelinating neuroglia... basically the 1st even to go wrong, damage usually done here
- secondary damage: axons --> poor neurotransmitters; causes cognitive, sensory and motor problems... axons are naked where they shouldn't be naked... and axons can't effectively communicate
demyelination disorder: guillian-barre syndrome
- immune mediated loss of PNS myelin that causes impaired neurotransmission
- incidence: 1 in a million
- etiology: bacterial or viral infection (respi or GI) or vaccine
- symptoms: progressive paralysis, but 70% of people usually resolve this problem... starts hard but eventually goes away
- treatment: (1) plasmapheresis... basically wash plasma to get rid of antibodies since the immune cells are doing the damage; (2) supportive treatment - ex glucocorticoid to decrease infection
demyelinated disorder: multiple sclerosis
- immune mediated loss of CNS myelin
- incidence: 1 in 1000... if you're in 3rd decade of life... females have a 2-4X more chance... if you have a 1st degree relative, 15X more chance... geographic location at first 15 yrs of life, farther from equatior are more likely to get this
- etiology: (a) immune disease, (b) viral mimicry
- contributing factors: sunlight, diet, genetics and hormones (so better to get more sun, eat more fish, get more vitD and male)
- pathology: chronic T cell-mediated demylenation of axons... cytokines recruit macrophage which stirs things up and does further damage... peri-neuronal scarring... impaired neurotransmission... periods of remission
- treatment: glucocorticoids to decrease inflammation, interferon-beta to decrease immune system, muscle relaxants to decrease twitching and tetani
review: which ions are more on the inside and more on the outside of the cell???
- more Na+ outside
- more Cl- outside
- more Ca2+ outside
- more K+ inside
- more A- inside
A- = negatively charged proteins, polypeptides, organophosphates that can't migrate across the membrane (DNA, RNA, etc...)
concentration gradient for individual ions across the selectively permeable cell membrane
- ionic gradient aka chemical gradient
- causes the membrane to be polarized... the differences across the membrane is energy waiting to be utilized
the inside of the cell is more negatively charged, ex -70mV for neurons
membrane potential of an undisturbed cell
- resting membrane potential
- is 'consistent' but ions are always moving across membrane
- so basically stays around 70mV even though ions are constantly moving in and out
what creates the membrane potential??? why is the cell interior more negative???
- 1. permeability: K+ is more permable than Na+ so more K+ leak channels take K+ OUT of the cell... loss of positively charged K+ inside the cell (aka more positively charged K+ outside)
- 2. Na+/K+ pump: 2K+ inside, 3Na+ outside = more positively charged cell exterior
- 3. fixed negatively charged proteins: A- are stuck inside the cell
differential distribution of ions across cell membrane
differential distribution of charge across cell membrane; opposites attract (think of magnets)
- electrical gradient
- electrical gradients can either reinforce or oppose the chemical gradient for each ion
chemical gradient + electrical gradient!!! chemical gradients and electrical gradients have the potential to do work... they're combined forces that influence the movement of ions
- ELECTROCHEMICAL GRADIENT
- ECG for K and Na are the primary factors affecting membrane potential!!!
describe what happens to K and Na during (1) chemical gradient, (2) electrical gradient, (2) overall electrochemical gradient
- K chemical: a lot of K+ exits (down chemical gradient)
- K electrical: little K+ enters (because inside of cell is more negative)
- K electrochemical: K+ exits
- Na chemical: a lot of Na+ enters (down chemical gradient)
- Na electrical: little Na+ enters (because of negative charge inside)
- Na electrochemical: A LOT MORE Na+ enters (if it could)
equal but opposite chemical and electrical gradients; driving force of gradient AND ion charge are opposite but equal? this potential for every ion is different!
- EQUILIBRIUM POTENTIAL
- reminder: at rest the membrane permeability for K is high and Na is low
what would happen if the membrane became a lot more permeable to Na?
Na+ would rush into cell moving toward equilibrium potential and makes the cell more positive
charge across membrane is less polar; membrane potential shifts toward a more positive one; positive ions (Na) rush into the cell; membrane potential moves from -70mV --> -60mV --> 0mV --> +40mV
re-stores resting membrane potential; gets back to -70mV; positive ions (Na and K) leave the cell
membrane potential moves away from 0; cell interior becomes more negative than normal resting membrane potential; positive ions (K) leave cell (efflux) ORRRRR negative ions (Cl) enter; decreases the chances of generating an action potential because further from the likelihood of reaching threshold
graphical representation of depolarization, repolarization and hyperpolarization:
ligand gated channels VS voltage gated channels in relation to neurons???
- ligand gated channels: in dendrites and soma... results in graded potential (red area on graph)
- voltage gated channels: in axon... results in action potential (green area on graph)
remember: voltage gated Na channels have an activation and inactivation gate that function independently
how does presynaptic cell communicate with postsynaptic cell?
- SYNAPTIC ACTIVITY
- basically, neurotransmitter released which then binds to postsynaptic receptors on B
what causes presynaptic cell to release neurotransmitter at synapse?
- ACTION POTENTIAL
- happens all the way down length of axonal projection
membrane potential of a cell in 'action;' rapid, large depolarization followed by repolarization at the membrane potential; (1) transmits electrical signal long distances, self regenerating at nodes, (2) AP will only happen if threshold is reached
membrane potential (-60mV for neurons) at which many voltage gated Na channels open up to initiate an action potential; Na can rush in cell to generate action potential if this is reached
- action potential can't take place w/o reaching threshold
- impt to remember: not every depolarization is big enough to reach threshold and result in an action potential
what causes action potentials?
how do graded potentials generate an action potential?
- key = threshold
- enough or strong enough graded potentials are generated such that threshold is reached
graded potential... basic characteristics???
- a local change in membrane potential that occurs in dendrites, some and axon hillock
- stimulus opens a ligand or mechanical gated channel
- local current... change in membrane potential doesn't travel far, it only affects local regions of cell membrane
- can be DEpolarizing or HYPERpolarizing because it depends on what channel is actually opened (Na or K or Cl)
- many different types of cells have graded potentials... ex motor end plate and glands
- it DECAYS as it moves... it's only a short distance signal and doesn't regenerate
- neighboring cells become depolarized bec of Na going in and it dissipates slowly... affects stuff next to it depending how close it is to the localized area
- graded potentials are smaller (smaller change in mV) compared to an action potential
- magnitude of depolarization depends on amount of stimulus (larger, longer, stimulus leads to a larger, longer graded potential)
- can be summed to reach threshold... graded potentials are additive!!! can combine to all lead to an action potential
self generating wave of electrochemical activity due to opening of many voltage gated Na channels on the axon; dramatic change in membrane potential (from -60mV to +30mV)
action potential... basic characteristics???
- only occurs in excitable membranes... ex in neurons and muscle fibers... begins at initial segment and travels down axons
- regenerated at unmyelinated regions (nodes) of axons
- always DEpolarizing!!! (remember: difference... graded can be de or hyper!)
- all or non response... once threshold is reached, can't loo back!
- magnitude of stimulus is 'negligible': maximum membrane potential is +30mV... can't get any more depolarized than this (diff from graded!!!)
- doesn't decay!!! long distance signal that regenerates at nodes, duration is always the same in a given tissue (diff from graded!!!)
depolarization positive feedback?
- graded potentials increase the amount of intracellular Na to cause further depolarization... neuron may now be depolarized enough to reach threshold
- at threshold, there is enough Na inside the cell via graded potentials, to open voltage gated ion channels to cause an action potential
- POSITIVE FEEDBACK = adding more Na inside causes more voltage gated Na channels to open!!!
generation of an action potential: what happens during DEPOLARIZATION???
- ligand or mechanical gated Na channels open at SOMA: causes Na to enter soma and create a local current, graded potentials are generated at hillock, membrane potential approaches -60mV
- action potential BEGINS as voltage gated Na channels open up at initial segment open (activation gate opens)... Na floods into neuron and membrane potential moves from -60mV to +30mV... triggers voltage gated Na channels to open all along axon (propagation of AP)
generation of an action potential: what happens during REPOLARIZATION??
- 1. neuron membrane potential starts at =30mV
- voltage gated Na channels close via inactivation gate and no more Na enters cell
- voltage gated K channels open and K rushes out of cell to bring down to resting membrane potential
- 2. neuron membrane potential at -70mV and goes to -90mV
- voltage gated K channels slowly shut and membrane potential reaches -90mV (hyperpolarization!!!)
3. Na/K pump normalizes levels to return to -70mV
4. neuron is now ready for another action potential
... can generate 1,000 action potential per second
when neuron absolutely can't generate another action potential; voltage gated Na channels need to fully recover
ABSOLUTE REFRACTORY PERIOD
neuron can generate another action potential if stimulus is strong enough; when hyperpolarized!; BUT stronger stimulus is needed to reach threshold
RELATIVE REFRACTORY PERIOD
graphical representation of absolute refractory period and relative refractory period: