Lecture 3 - Action Potential Conduction and Synaptic Transmission Flashcards
What are the three things that cause an action potential to move slowly? What are the correct terms for them?
- The axon is Leaky: Low Membrane Resistance (Rm)
- The axon is Thin: High Axial Resistance (Ra)
- The axon is Sticky: High Membrane Capacitance (Cm)
What solution did Invertebrates evolve to speed up action potentials?
Invertebrates (animals without a spinal cord) evolved a wider axon, giving a bigger surface for ions to flow
What solutions did Vertebrates evolve to speed up action potentials?
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)
How many voltage gated sodium channels are at each node of a myelinated axon?
1000-2000 at each node
How many voltage gated sodium channels are at each node of an unmyelinated axon?
100-200 at each node
What are nodes of Ranvier and what are their purpose?
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
Who discovered Nodes of Ranvier?
Louis-Antoine Ranvier
What is the link between axon diameter and AP conduction velocity?
A thicker diameter means it has myelin which makes it faster
What makes up the CNS myelin?
Oligodendrocytes, they have many branches
What makes up the PNS myelin?
Schwann Cells, they wrap around themselves
What is MS and what causes it?
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
What other disease is MS related to?
Epstein-Barr virus
Is MS genetic?
Yes. Identical Twins: 30%, Fraternal Twins: 4%
What are symptoms of MS?
Affects:
- Speech
- Vision
- Tactile
- etc.
Where and in who is MS prevalent?
3x more prevalent in women than men, and more prevalent in North America
What disease is like MS but in the PNS and how is it similar?
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
What did Santiago Ramon y Cajal discover?
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
How wide is the synaptic cleft?
20-40 nm
What was Loewi’s experiment and what did it help prove?
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.
Who discovered the quantal release of neurotransmitters?
Bernard Katz
How was the quantal release of neurotransmitters discovered?
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.)
What is the distribution of neurotransmitter release called?
Poisson distribution
How many quantas are released at 0.8 mV?
2
What is the difference between the synapse at rest and an active synapse?
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
What are the two ways Ca++ stays outside of the cell?
There is more Ca++ outside the cell than inside
- Ca++ pump: 2 H+ pumped in the cell, and 1 Ca++ out
- 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
What did Lily Jan and Yuh Nung Jan discover?
They discovered that peptides can be neurotransmitters
What are the three most common neurotransmitters?
- Glutamate: Most common excitatory NT
- GABA: Most common inhibitory NT in the cerebral cortex
- Glycine: Most common inhibitory NT in the brainstem
What is GABA permeable to?
GABA is primarily permeable to Cl- causing IPSPs (the cell gets really negative and far from threshold)
What is Glutamate permeable to?
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.
What are the four steps of the molecular mechanism for transmitter exocytosis
- Vesicle Docks (Synaptobrevin, synaptotagmin, SNAP-25, syntaxin)
- Entering Ca++ binds to synaptotagmin
- Snare complexes form to bring membranes close together
- Ca++ binded synaptotagmin catalyzes membrane fusion
What is the driving force equation and what does each part mean?
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
When solving the driving force equation, what does a negative and positive current mean?
A positive current: “outward” flow, cell is losing (+) charge
A negative current: “inward” flow, cell is gaining (+) charge
What is the name of when EPSPs are separated by space and not time?
Spatial summation, or spatial integration of EPSPs
What is the name of when EPSPs are separated by time and not space?
Temporal integration of EPSPs
What equations represented spatial integration of EPSPs?
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)
What equations represented temporal integration of EPSPs?
Time constant = RmCm
Vx = V0e^(-t/time constant)
Concerning EPSPs and IPSPs what is the most common event in real life?
Spatiotemporal integration of EPSPs and IPSPs
What did Neher and Sakmann discover?
They discovered the closing and opening of single ion channels using a patch clamp
What are are the four possible steps during a patch clamp?
- Cell attached: there is a mild suction using the recording pipette, and tight contact between the pipette and the membrane
- Inside-out: cytoplasmic domain accessible, and intracellular fluid now made available for manipulation
- Whole cell: strong pulse of suction, giving access to the entire cytoplasm
- Outside-out: the membrane breaks and then reseals, but extracellular domain is now accessible
What are the two types of axonal transports and their speeds?
- Fast axonal transport: 200-400 mm/day
- Slow axonal transport: 0.2-8 mm/day
What are the two directions axonal transports?
Anterograde: Movement from the cell body to the axon terminal
Retrograde: Movement from the axon terminal back to the cell body
What is another substance other than an NT is carried from the cell body to the axon terminal?
E.g.: Mitochondria
Is glutamate transported by axon terminal?
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.
How many mm is 1 um?
10^-3 mm (10^-6 m)
How many m is 1 nm?
10^-9 m
What would you use each patch clamp configuration?
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
