Lectures 8 & 9 Outline Flashcards
Anatomical organization of the NS
- billions of cells
- neurons & glia are specialized for communication (& info processing - which is what the NS does)
Functional organization of the NS
i) CNS
(1) Brain
(2) Spinal Cord
ii) Afferent (sensory) NS
(1) Touch, taste, smell, sound, sight input from enteric NS
iii) Efferent (output, control) NS
(1) Somatic Motor Neurons
(a) Skeletal Muscle
(2) Autonomic Motor Neurons
(a) Sympathetic
(b) Parasympathetic
Together control: cardiac muscle, smooth muscle, exocrine glands, some endocrine glands, adipose tissue
Neurons are specialized to ______
carry electrical signals & communicate with other cells
Neurons features
Unique morphology
- axons, dendrites, etc
- can communicate with distant targets
High density of ion channels
Special transport mechanisms to move materials from one end to the other
- depend on cytoskeleton
Secrete signaling molecules (neurotransmitters & neurohormones)
Types of Neurons
Sensory Neurons
- pseudounipolar
- bipolar
Interneurons of CNS
- anaxonic
- multipolar
Efferent Neurons
- multipolar
Anatomy of a neuron
- Dendrites
- Axon Hillock (initial segment or trigger zone)
- Cell body & nucleus
- Node of Ranvier
- Axon
- Myelin Sheath (NOT present on all neurons)
- Axon branches (collaterals)
- Presynaptic terminals, with synaptic vesicles
- Synaptic cleft
- Post-synaptic cleft
6 types of glia
- Oligodendrocytes (CNS)
- Ependymal Cells (CNS)
- Microglia (CNS)
- Astrocytes (CNS)
- Satellite Cells (PNS)
- Schwann Cells (PNS)
Oligodendrocytes role
- myelinate axons
in CNS
Ependymal cells role
- line “ventricles”
- make neural stem cells
- in CNS
Microglia role
“immune cells” of CNS
Astrocytes role
- blood brain barrier
- trophic factors
- take up excess water & K+
- neural stem cells
- pass lactate to neurons
- in CNS
Satellite cells role
trophic factors
- in PNS
Schwann cells role
myelinate axons
- in PNS
Ion channels control…
electrical activity in neurons
What does an ion channel look like?
neurons contain a high density of ion channels
many types of ion channels - classified according to:
- ions they carry
- where on the cell they are located
- gating mechanisms
Ion channel gating mechanisms
- Voltage gated ion channel
- changes in MP open the channel
- “threshold”
- opened & closed by charges in MP - Receptor channels
- (=ligand gated ion channels)
- gate when they bind a ligand (neurotransmitter, cGMP…) - Phosphorylation gated
- undergoes a small conformation change that can allow some of those channels to open/close - Stretch gated
- opens & closes when the cell membrane is deferred - Temp gates
- cell membrane will open & close depending on changes in specific temps
What is the basis of electrical signaling?
opening & closing of ion channels (thus changing the flow of ions) causes rapid changes in MP
Graded Potentials
1) Signals communicated from one neuron to the next are GPS: postsynaptic potentials
2) Small, “subthreshold” changes in MP
3) Can be depolarizing or hyperpolarizing
4) Passive (do not regenerate)
5) Gradually dissipate as they travel through a cell
6) Proportional to the size of the stimulus
7) Caused by the flow of ions through a few ion channels
8) Can be summed
9) Can be long-lasting
How does the GP travel like a ripple on a pond?
- it moves outward from the source & degrades as it moves farther away
- takes time to get from synapse to the axon hillock
- eventually degrades to nothing
Why does the signal degrade?
(nothing to regenerate it)
- electrical resistance in the cytoplasm
- the cell membrane is leaky to ions
Action Potentials
1) Wave of depolarization that ACTIVELY PROPAGATES across neuronal membrane (=REGENERATIVE, NOT PASSIVE)
2) All or none
3) Fast! Lasts only a few milliseconds
4) Often called a spike, or abbreviated AP
5) Large amplitude, about 100 mV (from RMP to peak)
6) ALWAYS depolarizing
7) Requires the membrane be depolarized PAST a threshold
8) There is a refractory period
9) CANNOT be summed
10) In neurons, site of AP generation is the axon hillock
Describe the ionic basis of the AP
- RMP
- Cell is depolarized by GP
- Membrane depolarizes to threshold
- VG Na+ channels open quickly, Na+ enters a cell
- VG K+ channels begin to open, but slowly - Rapid Na+ entry depolarizes cell
- Na+ channels INACTIVE & slower K+ channels fully open
- K+ leaves cell
- K+ channels remain open & additional K+ leaves cell, hyperpolarizing it (afterhyperpolarization)
- VG K+ channels close, less K+ leaks out of the cell
- Na+ channels begin to recover - Cell returns to resting ion permeability & RMP
- Na+ channels mostly recovered
During the afterhyperpolarization:
(caused by K+ leaving the cell), the two Na+ channels gates reset to their og positions (this is called recovery from inactivation)
this process takes a few milliseconds
recovery from inactivation is critical in determining refractory periods
Voltage-gated Na+ channels are the basis of the AP. They have 3 states…
- Activated (=open)
- Inactivated
- Closed
What are the 5 phases of the AP?
- Resting Potential
- Threshold
- Rising Phase
- Falling Phase
- Recovery Phase
Define Refractory periods
a period of time where you can’t fire an AP or it is much more difficult to fire an AP
Absolute refractory period
is the period during which a cell can absolutely NOT fire another AP
- happens when a cell starts to fire an AP in the rising phase. why? b/c during the rising phase all the Na+ channels are already opening as fast as they can
Relative refractory period
some of the Na+ channels are still inactivated but NOT ENOUGH of them to be able to fire an AP easily
- IOW, enough have recovered to be able to fire an AP, but the cell has to be stimulated more strongly than it did a the beginning in order to fire that AP (b/c a significant amount of those Na+ channels are not available they are inactivated)
Key role of Na+/K+ ATPase
- Na+/K+ ATPase –> only plays a role in establishing & maintaining the RMP
- Na+ may change by 0.00017%
- under normal physiological circumstances, the Na+ concentration inside the cell does not change
Describe single, tonic & bursting APs
Single AP - will wait a period of time & then it will fire another AP (most similar to normal APs)
Tonic AP - some neurons fire APs all by themselves
- don’t need any GPs to stimulate their MP to get to a threshold
- the neuron is just firing spontaneous APs (one after another, after another)
Bursting AP - will fire a couple of APs, then you get an afterhyerpolarization, then eventually it depolarizes enough to fire another couple APs
- literally fires them in bursts
Influence of extracellular K+
- Normal conditions (RMP is @ -70mV)
- small stimulus was not enough to bring it to the threshold, so it doesn’t fire an AP - But with a stronger stimulus it brought the cell to the threshold & then it fired an AP
- Hyperkalemia: increased extracellular K+ concentration
- then you depolarize the MP
- kidney failure for ex
- you are bringing it closer to the threshold to fire an AP so now the small stimulus IS enough to bring it to the threshold & you get an AP
* can cause increased excitability or an increased ability to fire APs - Hypokalemia: decreased extracellular K+ concentration
- then it will hyperpolarize the MP & the large stimulus that previously went past the threshold is not long (large enough) to get to the threshold
- therefore, you don’t see an AP, where you might have seen one before
* can lower excitability or make it harder to fire APs
APs in the unmyelinated axon
- Initial state: normal ion gradients, RMP ~ -70mV
- very high density of Na+ channels at the Axon Hillock (trigger zone)
- VG Na+ & K+ channels distributed along the axon - During an AP, Na+ rushes into the axon causing depolarization
- Some Na+ is attracted to the nearby areas (local current flow)
- this causes depolarization of the nearby axon to ITS threshold (the hillock is now recovered) - Na+ enters, causing depolarization
- again local current depolarizes the adjacent segment to threshold
- AP moves down the axon as a traveling wave of depolarization
Factors that influence axonal AP conduction
- Myelination
- increases velocity b/c insulated areas mean less leakage of Na+ & K+
- also means less ATP used
- myelination allows axons to be smaller, so you can fit more into a space - Increase axon diameter
- increases velocity b/c as the axon radius becomes larger, internal resistance decreases (inverse square relationship)
** large diameter axons can really speed up axonal conduction of AP, but myelination allows even faster conduction in less space
Differences b/t peripheral & central myelin
PNS: Schwann cells
- each Schwann cell wraps around a length of the axon sort of like a cinnamon roll (just curls around & around & around making an insulating layer)
- think cinnamon roll
CNS: Oligodendrocytes
- can form a myelin sheath on a # of different axons
- think octopus
Describe myelin features
- myelin is formed from concentric layers of glial cell membrane (in development)
- layers of membrane are excellent insulators (prevent the conduction of ions out of the axon - prevent the leakage of ions)
- very few ion channels myelin sheaths, or in the axonal membrane beneath (few leak or VG)
- myelination increases electrical efficiency of the axons (more faster & more robust - less chance an AP will fail)
- up to 200 layers!
Density of ion channels is much _____
Density of channels @ the nodes of ranvier tend to be really ____
lower
high
APs in the myelinated axons
myelin sheath form insulating segments along axon
- formed by concentric layers of glial cell membranes compacted together
separated by nodes of ranvier
Na+ channels found at very high density at nodes of Ranvier, K+ channels found nearby
instead of traveling as a wave, the action JUMPS from node to node: Saltatory Conduction
- b/c of this they travel much faster
Describe what happens to APs in demyelinating diseases
conduction slows when current leaks out of the previously insulated region b/t the nodes
- a depolarization that comes down the axon will stimulate an AP there, but then when that depolarization tries to travel in this newly unmyelinated area, it causes a leakage of ions out through the membrane & the AP WILL FAIL
(NEUROlogical consequences from this: loss of info from where that info is supposed to travel) - no longer have layer of insulation in this region of axon & so end up with more leakage of the ions after you lose that myelin sheath
- won’t be effectively conducted b/c very few VG Na+ channels (not enough to actively propagate an AP)
What is the neurological consequence of the demyelinating diseases?
NEUROlogical consequences from this: loss of info from where that info is supposed to travel)
Demyelinating disease - Multiple sclerosis
- autoimmune disease
- unknown cause: environment, virus, genetics, cerebral blood flow
- demyelination of CNS axons
- multiple patterns of progression: relapsing-remitting & several progressive phases
- symptoms include loss of balance, loss of speech, loss of vision, abnormal pupil reflexes, numbness, pain (SYMPTOMS ARE HIGHLY VARIABLE)
- treatments include immunosuppressants, other drugs as indicated by symptoms
Demyelinating disease - Guillain Barre syndrome (also acute inflammatory demyelinating polyneuropathy, AIDM)
- autoimmune, days after a seemingly minor GI or lung infection
- may be also associated with chronic illness such as lupus, HIV
- 1976 flu vaccine (1 additional case per 100 000)
- demylination of sensory, motor, & autonomic axons (PNS)
- slowing &/loss of AP conduction
- initial symptoms include tingling, weakness, pain in hands/feet
- symptoms may rapidly progress to inability to speak, paralysis, respiratory distress
- treatment may include plasmapheresis (to remove antibodies from blood) & immunoglobulin G (IGG) to inactivate circulating antibodies
- most people survive, recovery may take months to years
Diameter of an axon
all things being equal, a LARGER axon will conduct APs faster than a smaller diamater axon & all things being equal, a MYELINATED axon would conduct APs faster than a similarly sized nonmyelinated axon
Fugu Poison or Tetrodoxin (TTX)
(kills 30-100 people per year worldwide)
comes from pufferfish & several other species of animals
fugu is a very specific antagonist of VG Na+ channels
- high affinity, high specificity
- high efficacy, high potency
prevents entry of Na+ into cells
prevents APs in neurons & muscle
lidocaine, benzocaine & other local anesthetics also block VG Na+ channels
