Exam 2 - Action Potential and Neuro Intro

Question 1

Describe the propagation of an electrical signal by fast sodium channels?

Answer 1

A stimulus depolarizes a section of the cell that opens fast sodium channels. The singal travels both directions along the cell depolarizing the membrane and opening more sodium channels.

Question 2

Descibe the how the propagation of a signal in repolarization occurs?

Answer 2

Fast Na+ channel close quickly and potassium channels open, repolarizing the cell in the same direction as the depolarization.

Question 3

What type of feedback is used during opening of Na+ channels during depolarization?

Answer 3

Positive feedback

Na+ opening causes depolarization and more Na+ channels to open.

Question 4

What structure(s) allow communication between the brain and muscles?

Answer 4

Motor neurons and release of neurotransmitters at the neuromuscular junction (NMJ).

Question 5

Describe the nACh receptor/channel?

Answer 5

A protein at the NMJ that has 2 binding sites for acetylcholine (neurotransmitter). The inside of the protein is lined with negatively charged amino acids that repel negatively charged ions (positvely charged ion specific). The majority of the current is Na+ that starts the action potential. Small amount of K+ leaks out but is mitigated by Na+ influx. Ca+ also can come in and depolarize the cell, but is large and doesn’t come in as readily as Na+.

Nicotine can simulate Ach and causes tremors.

Question 6

Describe how nAch receptors can lead to depolarization of the cell?

Answer 6

2 Ach have to bind to open the negatively charged pore and allow the positive charge in (usually Na+). This sets off the fast Na+ channels the are next to the Ach receptor.

Question 7

Why are NMJ inportant for us to know about?

Answer 7

This is where our paralytics work.

Question 8

Describe mAch receptors and their function during hyperpolarization?

Answer 8

Found in the heart and mediates pumping by hyperpolarization. They are GPCRs and are activated by acetylcholine, the alpha subunit activates K+ channels which causes K+ to leave the cell making it more electronegative. This makes Vrm more negative (hyperpolarized) and makes it take longer to reach an action potential.

Named because they respond to a substance called muscarine.

In the heart, this process maintains HR and with vagal stimulation slows HR down even more.

Question 9

How are the AV and SA node innervated?

Answer 9

The left vagus nerve attaches to the AV and the right vagus nerve attaches to the SA.

Question 10

How do antimuscarnics work? What effect do the have in the heart?

Answer 10

They antagonize mAch receptors, which prevents K+ channels from opening making Vrm more positive, leading to shorter time to fire an action potential and more BPM.

Ex: Atropine - blocks vagus activity in the HR

Question 11

Describe how physical pressure can turn a neuron on?

Answer 11

There are baroreceptors that sense pressure in cells. Increased pressure causes widening of pressure sensitive Na+ channels that leads to influx of Na+. If cell become positive enough, it will lead to an action potential that goes back to the brain/brainstem for processing.

More pressure = more Na+ influx

Question 12

Define threshold?

Answer 12

The charge that a stimulus must depolarize the cell to in order to fire an action potential.

Not all cell’s have same threshold

Question 13

What is sub-threshold?

Answer 13

A stimulus that does not overcome the cell’s threshold and will not fire an action potential.

Question 14

What would an action potential look like for a weak stimulus that barely meets threshold?

Answer 14

There can be a delay in firing the action potential; slower firing of the action potential.

Question 15

What is supra-threshold?

Answer 15

A strong stimulus that depolarizes the cell well above threshold, leading to a faster action potential.

Question 16

How do action potentials in the heart differ from other action potentials?

Answer 16

The action potentials take longer and are sustained (plateau) to allow effective pumping. This is due to slow Ca++ channels.

Question 17

What is the role of Cl- in the nervous system?

Answer 17

Permeability is adjusted to hyperpolarize or supress excitable cells. This occurs via GABA receptors that open chloride channels in neurons; prevents overactivity like seizures.

“Brakes” of the nervous system

Question 18

Describe calcium’s role in action potentials?

Answer 18

Calcium is large, has double positive charge, and huge concentration gradient. So, it sits near the cell wall and will block Na+ leak channels, blunting cell electrial activity.

Results in a “calming effect”, by stabilizing membrane potentials

Question 19

What effects would hypocalcemia have on the cells membrane potential?

Answer 19

Hypocalcemia results in an increase in Na+ influx through Na+ leak channels (because less Ca ions are blocking the channel). This makes the cell less polar and makes the membrane potential more positive (more excitable).

Question 20

What happens to membrane potential during hyperkalemia? How can this be corrected?

Answer 20

K+ will not leave the cell as much leading to a more positive membrane potential.
Giving Ca++ will block Na+ leak channels make the cell less positive, opposing the effects of hyperkalemia.

Question 21

Wy doesn’t Ca++ also block K+ leak channels?

Answer 21

Because K+ is leaving the cell, so Ca++ will just be moved out of the way.

Question 22

What effect does hypocalcemia have on motor neurons? What clinical sign does this cause?

Answer 22

Leads to a more positive resting potential and will cause hyperactivity of the motor neuron, leading to tetany.

Trusseau sign and Chvostek sign

Question 23

What other compound can aid in reducing cell hyperactivity (increased membrane potential)?

Answer 23

Mg++ helps to hyperpolarize the cell; provides similar effects to Ca++, but mechanism is not clear.

Question 24

What effects the rate of electrial propagation in nerve fibers?

Answer 24

1. Length of the nerve (longer nerve takes more time for signal to reach destination)
2. Diameter of the nerve (Wider = Faster; less resistance)
3. Insulation (myelin sheath = faster)

Question 25

Where can myelin be derived from?

Answer 25

The sphingomyelin in the cell wall.

Question 26

What cell is involved in myelination in the periphery? How does it work?

Answer 26

Schwann cells. They wrap around the nerve in layers and as it does, all of the water is pushed out of the cell leaving a lipid compound that provides protection, speed, and efficency for neurons.

Question 27

How is an action potential spread?

Answer 27

Through opening of fast Na+ channels. Na+ channels open causing depolarization that cause more Na+ channels to open.

Question 28

What are the effects of myelination of nerve fibers?

Answer 28

1. **Speeds up rate of signal** by blocking Na+/K+ pumps, preventing loss of Na+ and continuation of the signal. 2. **Reduces cell energy** requirements because Na+/K+ pumps are not running as much. ***Less prone to ischemia***. 3. **Protection** from injuries or other forces.

Question 29

What are the openings in between myleinated nerve fibers called?

Answer 29

Nodes of Ranvier

Question 30

What is important about the nodes of ranvier?

Answer 30

There is a high density of fast Na+ channels that help ensure the continuation of the signal to the next myleinated nerve fiber. (saltatory conduction)

Question 31

What is one difference between myelinated and unmyelinated neurons?

Answer 31

Unmyelinated neurons have much more fast Na+ channels along them than unmyelinated neurons. ##Footnote Although they may not have more overall.

Question 32

Why would a myelinated nerve fiber require MORE local anesthetic to block than and unmyelinated nerve?

Answer 32

Because of the high density of fast Na+ channels at the nodes of ranvier.

Question 33

What is saltatory conduction?

Answer 33

The "jumping" of an action potential from one node of ranvier to the next, due to Na+ being prevented from leaving the cell under the myelinated sections.

Question 34

What cells preserve and maintain myelin in the CNS?

Answer 34

Oligodendrocytes ## Footnote These cells are not good at replacing lost myelin

Question 35

What cells preserve and maintain myelin in the PNS?

Answer 35

Schwann cells ## Footnote Are able to replace some lost myelin much better than oligodendrocytes

Question 36

Describe what happens with demyelinating diseases?

Answer 36

When myelin is present the channels underneath the myelin will disappear beacuse they are not being used. When the myelin degrades, the Na+ and K+ channels are not replenished but, the Na/K/ATP pump is. So, during an action potential the Na channels are still far apart and the Na/K pump is in between pumping all of the Na back out, leading to inhibition of the signal which can result in paralysis.

Question 37

What are some demyelinating diseases and their causes?

Answer 37

MS, Optic Neuritis, Guillain-Barre Syndrome Causes: Genetics, infection, autoimmune hyperactivity

Question 38

What are gap junctions?

Answer 38

Gap junctions are small pores/channels that allow movement of small ions (mainly Na+) from one cell to a neighboring cell (both forwards and backwards). This is used in rapid transduction of an electrical signal. The more gap junctions, the faster the signal is moved from one cell to the next. ## Footnote The bidirectionality can be bad in the heart when a rogue electrical current can be allowed to move easily though gap juntions.

Question 39

What is the structure of a gap junction?

Answer 39

Comprised of 6 connexin proteins that make up a single connexon. 2 connexons lined up together make up the gap junction.

Question 40

What are the postsynaptic and presynaptic terminals?

Answer 40

Presynaptic is the sending cell. Postsynaptic is the recieving cell.

Question 41

What are the myelination classifications?

Answer 41

A: Myelinated B: Lightly myelinated C: Non-myelinated

Question 42

How does importance of a signal relate to nerve size?

Answer 42

The more important signals (motor functions) are sent through bigger, myelinated, neurons. Not so important signals are sent through smaller, unmyelinated neurons.

Question 43

What are the categories of A fibers? How are they classifed?

Answer 43

Alpha, beta, gamma, and delta. Classifed by size from largest to smallest.

Question 44

What is the soma?

Answer 44

The cell body of a neuron where the nucleus and lots of mitochondria are.

Question 45

What is the recieving structure in a neuron?

Answer 45

Dendrites

Question 46

Describe the membrane potentials in the excitatory portions of a neuron?

Answer 46

The dendrites have a more positve membrane potential than the rest of the cell that allows them to respond quickly to excitatory stimuli.

Question 47

Describe the membrane potentials in the inhibitory portions of a neuron?

Answer 47

The membrane potentials are more negative the rest of the cell.

Question 48

Describe the sending portion of a neuron?

Answer 48

The axon, most are myelinated but not at the presynaptic terminal so that neurotransmitters can be released.

Question 49

Describe the properties of the axon hillock?

Answer 49

The axon hillock is at the begining of the axon that is composed of inhibitory connections that suppresses the activity of the CNS via GABA.

Question 50

Describe how inhibition is accomplished at the axon hillock?

Answer 50

The hillock is comprised of inhibitory synapses that release GABA. GABA is the major inhibitory neurotransmitter and causes an incresase in Cl- permeability which results in hyperpolarization (inhibition/suppression).

Question 51

Describe the relationship between alcohol and GABA?

Answer 51

EtOH is GABA receptor agonist, which causes low production of endogenous GABA. When EtOH is taken away, there is not enough GABA to inhibit the nervous system leading to seizures.

Question 52

What are macro glial cells?

Answer 52

Astrocytes, ependymal cells, and oligodenrocytes.

Question 53

What is the role of astrocytes?

Answer 53

Important in the BBB by wrapping around the capillaries in the brain. They help maintain electrolyte and pH balance in the CSF.

Question 54

What is the role of ependymal cells?

Answer 54

They produce CSF and have cillia to move the CSF around.

Question 55

What is the role of microglia?

Answer 55

Digest debris that is within the CSF.

Question 56

Describe a multipolar nueron?

Answer 56

They are decision making cells. Decide wheter to fire AP or not. (Motor neuron)

Question 57

Describe a bipolar neuron?

Answer 57

Used in special organs for specialized senses. (Photoreceptors in retina and optic nerve).

Question 58

Describe a pseudounipolar neuron?

Answer 58

Majority of sensory function. Primarily just passing of information. Doesn't need to make decisions.

Question 59

What does the term somatic mean?

Answer 59

Conciously sensible

Question 60

What are the function of free nerve endings?

Answer 60

Sensing and sending pain signals. | Also called nociceptors.

Question 61

Describe the adaptability of baroreceptors?

Answer 61

They will reset (adapt) themselves after exposure to a prolonged stimulus (elevated blood pressure). This gives the body the ability to respond to new changes. If they didn't adapt, they would reach their limit for signal transduction.

Question 62

Why is fast adaption important?

Answer 62

Because the body cares more about new changes as opposed to staying focused on the one change. That way the nervous system is not overwhelmed with continual signaling.

Question 63

How many connections can a neuron have?

Answer 63

Some have 10,000+

Question 64

What is reverse adaptation? Where does this happen?

Answer 64

Is when cells do not reset or adapt to stimulus but become more sensitized instead. This happens with nociceptors. More pain = more sensitivity to pain.

Question 65

How can reverse adaptaion be managed?

Answer 65

Giving pain medication before the pain starts or by performing a nerve block. Once pain level is high it can be very hard to impossible to bring back down.

Question 66

How does a neuron propigate an action potential?

Answer 66

There are fast Na+ channels along the neuron that depolarize as the action potential moves down toward the synapse. There are VG K+ channels and Na+/K+ pumps also down the neuron to repolarize the cell. Once the neuron is depolarized to the terminal end, p-type Ca++ channels open which cause VP-2 vesicles to fuse with the membrane and release their contents.

Question 67

How are vesicles stimulated to release their neurotransmitter in a motor neuron? Explain the two types of vesicles in the neuron.

Answer 67

The action potential reaches the end of the neuron and open p-type calcium channels that allow Ca++ ions in. The Ca++ ions destabilze VP-2 storage vesicles that are close to the cell wall and cause them to empty ACh into the synapse. The VP-1 vesicles are futher away from the wall and are not ready to be activated.

Question 68

What processes reset the cell in a motor neuron?

Answer 68

1. The Ca++ ATP pump 2. Na+/K+ pump 3. VG K+ channels 4. Ca++ sensitive K+ channels

Question 69

Describe end plate potential?

Answer 69

The initial depolarazation caused by opening of nACh-R of the recieving cell at a synapse. In a healthy muscle, these will always turn into an action potential because of fast Na+ channels next to the nACh-R. This is possible because of the vast excess in number of receptors and neurotransmitters.

Question 70

How would our HR be affected if we did not have inhibition from mACh receptors?

Answer 70

Our heart would beat at about 120 bpm if there was no inhibition.

Question 71

What is the largest compartment in non-obese people?

Answer 71

The skeletal muscles

Question 72

What muscle cells are innervated by more than 1 motor neuron?

Answer 72

Occular muscles

Question 73

How many muscle cells does one neuron innervate?

Answer 73

Typically one cell, except for occular muscle

Question 74

What are the 2 ways a motor neuron can be activated?

Answer 74

1. By the descending spinal tracts from the brain 2. By the reflex archs

Question 75

What are the contractile elements in muscle fibers?

Answer 75

Actin and myosin, they cause the muscle fibers to shorten which results in contraction

Question 76

What is the specialized version of the endoplasmic reticulum found in skeletal muscle? What is its purpose?

Answer 76

Sarcoplasmic reticulum Primary source of calcium for muscle contraction

Question 77

Describe the length of muscle fibers?

Answer 77

They are usually very long, some are 1 foot in length.

Question 78

What is the function of transverse tubules?

Answer 78

Crosses the muscle fibers transversely allowing the action potential to travel deep into the tissue via fast Na+ channels and DHP receptors.

Question 79

Describe the location of mitochondria in a motor unit and neuron?

Answer 79

There are lots of mitochondria situated close to the clefts of the postsynaptic terminal. They are also inside of the presynaptic terminal of the motor neuron.

Question 80

What are the names of the indicated structures?

Answer 80

Primary clefts and secondary clefts

Question 81

Describe the location of ACh receptors and fast Na+ channels in the NMJ?

Answer 81

Acetylcholine receptors are situated near the top of the clefts and the VG Na+ channels are towards the bottom of cleft as well as spanning the length of the muscle fiber.

Question 82

Where is acetylchoninesterase found? How does it break down ACh?

Answer 82

Acetylcholinesterase is attached to the skeletal muscle cell It uses hydrolysis to break down an ester bond on ACh into Acetyl (acetate) and choline

Question 83

What type of macromolecule is acetyl or acetate?

Answer 83

Starch

Question 84

Where are schwann cell bodies located on a motor neuron?

Answer 84

They are situated near the end of the presynaptic terminal

Question 85

How many ACh receptors are present at the NMJ? How many are activated per action potential? How much Ach is released?

Answer 85

* 5 million ACh receptors * 500,000 activated per AP (10 % of receptors) * 1 million ACh molecules minimum (each receptor needs 2 ACh), usually 2 million are released (some are destroed by acetylcholinesterase before reaching receptor)

Question 86

Why doesnt much K+ leave through the ACh receptor during activation?

Answer 86

There is a lot of Na+ and Ca++ flooding in and there are lots of K+ leak channels that K+ can leave through instead

Question 87

What organic compound can block ACh receptors? What drugs are modeled after it? How do they work?

Answer 87

* Curare * NDMR * They block ACh from binding to the receptor, preventing depolarization (only one site has to be blocked to inactivated the receptor)

Question 88

How does the skeletal muscle detect an AP at the NMJ? How does lead to contraction?

Answer 88

Through DHP (dihydropyradine) receptors that are situated at the *NMJ and transverse tubules*. The receptors are tethered directly to Ca++ channels of the SR. They open these Ca++ channels when stimulated by an AP.

Question 89

What is the appearance of the DHP receptor? Can anything enter through them?

Answer 89

It looks like a VG Ca++ channel and a small amount of Ca++ does enter through them when activated.

Question 90

What are the names of the channels that DHP receptors open on the SR?

Answer 90

Ca++ release channel or RyR (ryanodine receptors)

Question 91

How is calcium put back into the SR after a contraction?

Answer 91

By the SERCA (Sacroplasmic Endoplasmic Reticulum Calcium ATPase) This pump needs to use energy to move Ca against its concentration gradient (lots of Ca in the SR)

Question 92

Describe the E-C coupling pathway in skeletal muscle?

Answer 92

* Motor neuron depolarizes due to AP sent by reflex arch or brain * Ca++ influx into MN by p-type Ca++ channels * ACh vesicles fuse to presynaptic terminal * ACh released into NMJ and binds to nACh receptors * Na+ and some Ca+ influx generates end plate potential (EPP) * EPP local depolarization leads to an AP * AP spreads lenghtwise down muscle fibers via fast Na+ channels * AP sensed by DHP receptors which cause release from RyR * Ca++ influx into sarcoplasm * Ca++ tucked back into SR by SERCA

Question 93

How is choline transported back into the neuron for recycling?

Answer 93

Choline ATPase and Choline Na+ transporter

Question 94

What is mitochodrias function in the neuron?

Answer 94

Source of ATP Storage of acetate for ACh production

Question 95

Where can extra choline be found in the neuron?

Answer 95

In the cell membrane from phosphatidylcholine

Question 96

Describe myaesthenia gravis and how it affects the NMJ?

Answer 96

* A person's body makes antibodies against nACh-R (because of a faulty thymus) * The antibodies sit on the receptors triggering the immune system to destroy them * This causes scare tissue on the clefts reducing the amount of surface area for nACh receptors and fast Na+ channels * This leads to the inability to propagate an AP and progressive muscle weakness | Disease usually gets worse throughout day

Question 97

What are the treatments for MG?

Answer 97

Thymus removal, plasmapheresis, acetylcholinesterase inhibitors (-stigmines)

Question 98

Describe LEMS/ELMS and how it effects the NMJ?

Answer 98

Lambert-Eaton Myaesthenic Syndrome *Oncology patients (usually lung) create antibodies against p-type calcium channels *Results in Ca++ defeciency in MN which does not allow ACh to be released by vesicles

Question 99

What are the treatments for LEMS/ELMS?

Answer 99

* AChesterase inhibitors will not work - Ach is not being released * Plasmaphereisis * Removal of lung tumors * K+ channel blockers (TEA - tetraethylammonium, 4,5-dihydropyradine) - these work by slowing repolarization which should allow more Ca++ in and cause ACh release

Question 100

Why are K+ channel blockers for LEMS/ELMS so dangerous?

Answer 100

They are not specific to only motor neuron K+ channels, they can effect channels all over body including the heart leading to cardiotoxicity

Question 101

Why is amiodoarone a safe K+ channel blocker?

Answer 101

Because it is not very specific for K+ channels, making it safer

Question 102

How do NDMR work?

Answer 102

They are nACh receptor antagonists, preventing ACh from binding and thereby preventing depolarization and muscle contraction.

Question 103

What is the main DMR and how does it work? What is its structure?

Answer 103

* Succinylcholine * Its structure is 2 acetylcholines attached to each other * Causes sustained depolarization at nACh receptors which prevents reseting of *local* fast Na+ channels (an AP cannot be generated at NMJ) * AChesterase is not effective at breaking down succinylcholine

Question 104

What will you see when succinylcholine is first adminstered and why?

Answer 104

* Fasiculations or twitching * Due to inital depolarization caused by activation of nACh receptors

Question 105

Describe the membrane potential change and its effects with succinylcholine administration?

Answer 105

* The membrane potential in the skeletal muscle is much more positive due to all of the Na+ influx through nACh receptors * This causes K+ to be pushed out of the cell * This normally leads to a 0.5 mOsm increase in serum K+

Question 106

How do deinnervating diseases or strokes lead to worse hyperkalemia with succinylcholine than normal?

Answer 106

In muscle that has not been used much, they usually have additional nACh receptors away from the NMJ. This leads to more muscle fibers being depolarized than just at the NMJ. This leads to a more profound exiting of K+ and worseing hyperkalemia.