Lecture 3 - Action Potential Conduction and Synaptic Transmission

Question 1

What are the three things that cause an action potential to move slowly? What are the correct terms for them?

Answer 1

1. The axon is Leaky: Low Membrane Resistance (Rm)
2. The axon is Thin: High Axial Resistance (Ra)
3. The axon is Sticky: High Membrane Capacitance (Cm)

Question 2

What solution did Invertebrates evolve to speed up action potentials?

Answer 2

Invertebrates (animals without a spinal cord) evolved a wider axon, giving a bigger surface for ions to flow

Question 3

What solutions did Vertebrates evolve to speed up action potentials?

Answer 3

Vertebrates (animals with a spinal cord) evolved myelin to reduce leakiness (myelin blocks a lot of channels like the K+ leak channels), and stickiness (myelin physically separates ions of opposite charges)

Question 4

How many voltage gated sodium channels are at each node of a myelinated axon?

Answer 4

1000-2000 at each node

Question 5

How many voltage gated sodium channels are at each node of an unmyelinated axon?

Answer 5

100-200 at each node

Question 6

What are nodes of Ranvier and what are their purpose?

Answer 6

Nodes of Ranvier are gaps on the axon with no myelin that allow the action potentials to regenerate, without them, Na+ and K+ channels would have to continuously regenerate action potentials and that would make action potential propagation much slower

Question 7

Who discovered Nodes of Ranvier?

Answer 7

Louis-Antoine Ranvier

Question 8

What is the link between axon diameter and AP conduction velocity?

Answer 8

A thicker diameter means it has myelin which makes it faster

Question 9

What makes up the CNS myelin?

Answer 9

Oligodendrocytes, they have many branches

Question 10

What makes up the PNS myelin?

Answer 10

Schwann Cells, they wrap around themselves

Question 11

What is MS and what causes it?

Answer 11

Multiple Sclerosis is a condition where the myelin on the axon begins to degenerate

It occurs randomly, and symptoms can appear one day and disappear the next as the CNS tries to repair itself

MS is autoimmune, and occurs when a virus enters the body having a protein that looks similar to a protein component of myelin, and as a result the body begins attacking the myelin instead of the virus

Question 12

What other disease is MS related to?

Answer 12

Epstein-Barr virus

Question 13

Is MS genetic?

Answer 13

Yes. Identical Twins: 30%, Fraternal Twins: 4%

Question 14

What are symptoms of MS?

Answer 14

Affects:
- Speech
- Vision
- Tactile
- etc.

Question 15

Where and in who is MS prevalent?

Answer 15

3x more prevalent in women than men, and more prevalent in North America

Question 16

What disease is like MS but in the PNS and how is it similar?

Answer 16

Guillain-Barre Syndrome, it is also autoimmune and attacks Schwann cells of myelin, and it causes difficulty breathing, swallowing, paralysis and 30% of people need ventilators

Question 17

What did Santiago Ramon y Cajal discover?

Answer 17

He discovered that there is a gap between neurons (between the presynaptic terminal and the post-synaptic cell), which we now know as the synaptic cleft

Question 18

How wide is the synaptic cleft?

Answer 18

20-40 nm

Question 19

What was Loewi’s experiment and what did it help prove?

Answer 19

He proved that neurotransmitters get released at the end of an axon and did so by placing on frog heart in saline solution and connecting the solution to a different tub where he placed the second frog heart. He then shocked the vagus nerve of the first heart and observed the heartbeat slow down. To his surprise, even without shocking the second heart, its heart beat also slowed down, proving that something was being released into the fluid, having an effect on the second heart too.

Question 20

Who discovered the quantal release of neurotransmitters?

Answer 20

Bernard Katz

Question 21

How was the quantal release of neurotransmitters discovered?

Answer 21

An axon with a low extracellular Ca++ concentration (in order to avoid the likelihood of individual neurotransmitters being released and get small muscle contractions) was stimulated, and it was seen that there were peaks at 0.4 multiples, meaning that neurotransmitters were getting released in packets (many trials resulted in 0.4 mV amplitudes, 0.8 amplitudes, etc.)

Question 22

What is the distribution of neurotransmitter release called?

Answer 22

Poisson distribution

Question 23

How many quantas are released at 0.8 mV?

Answer 23

2

Question 24

What is the difference between the synapse at rest and an active synapse?

Answer 24

In the synapse at rest the VgCaC is closed meaning no neurotransmitters are being released and biding to receptors to let in the CNS fluid ions into the postsynaptic cell/dendrite

In the active synapse the action potential reaches the axon terminal and triggers the opening of the VgCaC and allowing the cascade of events to occur

Question 25

What are the two ways Ca++ stays outside of the cell?

Answer 25

There is more Ca++ outside the cell than inside 1. Ca++ pump: 2 H+ pumped in the cell, and 1 Ca++ out 2. Na+/Ca++ exchanger: The energy of one thing is used for another thing, so the inward movement of Na+ (it is going with its concentration gradient) provides energy to allow Ca++ to go against its concentration gradient

Question 26

What did Lily Jan and Yuh Nung Jan discover?

Answer 26

They discovered that peptides can be neurotransmitters

Question 27

What are the three most common neurotransmitters?

Answer 27

1. Glutamate: Most common excitatory NT 2. GABA: Most common inhibitory NT in the cerebral cortex 3. Glycine: Most common inhibitory NT in the brainstem

Question 28

What is GABA permeable to?

Answer 28

GABA is primarily permeable to Cl- causing IPSPs (the cell gets really negative and far from threshold)

Question 29

What is Glutamate permeable to?

Answer 29

Glutamate is equally permeable to both Na+ and K+ causing EPSPs (note that if the binding of NTs cause depolarization of the postsynaptic membrane, an action potential can occur there) Note that the driving force cause Na+ to enter is greater than the driving force causing K+ to leave, resulting in an AP.

Question 30

What are the four steps of the molecular mechanism for transmitter exocytosis

Answer 30

1. Vesicle Docks (Synaptobrevin, synaptotagmin, SNAP-25, syntaxin) 2. Entering Ca++ binds to synaptotagmin 3. Snare complexes form to bring membranes close together 4. Ca++ binded synaptotagmin catalyzes membrane fusion

Question 31

What is the driving force equation and what does each part mean?

Answer 31

Ix = gx (Vm-Ex) --> used to calculate the flow of an ion Ix = current of an ion gx = membrane conductance (similar to Px) Vm = membrane potential Ex = ion equilibrium potential Vm-Ex = driving force

Question 32

When solving the driving force equation, what does a negative and positive current mean?

Answer 32

A positive current: "outward" flow, cell is losing (+) charge A negative current: "inward" flow, cell is gaining (+) charge

Question 33

What is the name of when EPSPs are separated by space and not time?

Answer 33

Spatial summation, or spatial integration of EPSPs

Question 34

What is the name of when EPSPs are separated by time and not space?

Answer 34

Temporal integration of EPSPs

Question 35

What equations represented spatial integration of EPSPs?

Answer 35

Lamda (or distance constant) = square root of Rm/Ra Vx = V0e^(-x/lamda) *in all cases, V0 is the change in potential (e.g. -65 mV to -55 mV means V0 = +10 mV)*

Question 36

What equations represented temporal integration of EPSPs?

Answer 36

Time constant = RmCm Vx = V0e^(-t/time constant)

Question 37

Concerning EPSPs and IPSPs what is the most common event in real life?

Answer 37

Spatiotemporal integration of EPSPs and IPSPs

Question 38

What did Neher and Sakmann discover?

Answer 38

They discovered the closing and opening of single ion channels using a patch clamp

Question 39

What are are the four possible steps during a patch clamp?

Answer 39

1. Cell attached: there is a mild suction using the recording pipette, and tight contact between the pipette and the membrane 2. Inside-out: cytoplasmic domain accessible, and intracellular fluid now made available for manipulation 3. Whole cell: strong pulse of suction, giving access to the entire cytoplasm 4. Outside-out: the membrane breaks and then reseals, but extracellular domain is now accessible

Question 40

What are the two types of axonal transports and their speeds?

Answer 40

1. Fast axonal transport: 200-400 mm/day 2. Slow axonal transport: 0.2-8 mm/day

Question 41

What are the two directions axonal transports?

Answer 41

Anterograde: Movement from the cell body to the axon terminal Retrograde: Movement from the axon terminal back to the cell body

Question 42

What is another substance other than an NT is carried from the cell body to the axon terminal?

Answer 42

E.g.: Mitochondria

Question 43

Is glutamate transported by axon terminal?

Answer 43

Glutamate is not transported by axonal transport but instead is synthesized locally by glutamine in the terminal, since glutamine gets taken up from extracellular fluid by by an enzyme called glutaminase, and is then converted to glutamate.

Question 44

How many mm is 1 um?

Answer 44

10^-3 mm (10^-6 m)

Question 45

How many m is 1 nm?

Answer 45

10^-9 m

Question 46

What would you use each patch clamp configuration?

Answer 46

Cell attached: things like extracellular drug effect Inside-out: Intracellular ligand effect (but only in the case of single channel recording, when we want a small membrane patch, etc.) Outside-out: Extracellular ligand effect Whole cell: Intracellular manipulation effect on entire cell