Day 2 action potential
What are voltage gated potassium channels? What do they do? How are they different from voltage gated Na channels (3)
"Delayed rectifier" lack "ball and chain" so they are either closed or activated (there is no inactivated state) Cause the undershoot 1. Ion permeability K+ instead of Na+ 2. Very slow activation rate compared to Na+ 3. Lack fast inactivation bc they do NOT contain "ball and chain" structure
What two types of demyelinating diseases are there? Give examples for both? Why are there two types?
1. Affecting CNS- multiple sclerosis 2. Affecting PNS- Guillian-Barré syndrome Because CNS and PNS axons are myelinated by different classes of glia: CNS- oligodendrocytes PNS- Schwann cells
How does myelination affect action potential propagation?
1. Alters the distribution of ion channels in the axon membrane 2. Alters the length and time constants of the axon membrane
What happens to the sodium channels if the membrane is depolarized to threshold? (3 steps)
1. At first only a few voltage gated sodium channels allow in word sodium current to flow. 2. This in word current through these channels depolarizes the membrane more, causing more voltage gated sodium channels to open 3. #2 continues until almost all sodium channels in the cell membrane are open
What does the passive electrical properties of the axon determine?
1. How far along the axon the capacitive current spreads (length constant) 2. How rapidly the capacity of current depolarizes each membrane segment to threshold (time constant)
What two channels are involved in action potential's in neurons?
1. Na+ voltage-gated channels 2. K+ voltage-gate channels
What are the four phases of an impulse?
1. Rising phase 2. Overshoot phase 3. Falling phase 4. Undershoot phase
What are the two net effects of myelination?
1. Very rapid conduction velocity 2. Action potential jumps (saltates) from node to node
What are the three parts of the voltage gated sodium channels?
1. Voltage sensor 2. Pore 3. Inactivation particle or "ball and chain"
What is the absolute refractory period? What causes this? When does it end?
A period of time when a second action potential cannot be generated Caused by the end activation of voltage gated sodium channels. When enough voltage gated sodium channels have recovered from an activation so that another action potential can be generated
What is tetrodotoxin (TTX)?
A virulent poison from puffer fish which blocks voltage gated sodium channels, and is fatal at very low doses
What are action potentials that propagate in the backwards direction?
Antidromic
What determines the firing rate between threshold and maximum? How does this change with time?
At what point the refractory state is in. Early in the relative refractory period: the threshold current is large almost all delayed rectifier potassium channels are open and some of the voltage gated sodium channels remain in an in activated state. Over the course of the relative refractory period, as the voltage gated sodium channels finish recovering from an activation in the delayed rectifier channels close, the current required to reach threshold gradually returns back to normal.
When length constant is increased in myelination why is the time constant not affected?
Because the increase in membrane resistance (Rm) and the decrease in membrane capacitance (Cm) cancel each other out
When can weak stimulation trigger action potentials in the relative refractory period? When can stronger stimulation fire during relative refractory period? What will very strong stimulation fire?
Can only trigger firing late during the relative refractory period (bc The decay in threshold current) *resulting in a low rate of firing* Can cause firing earlier during the relative refractive period *Producing a higher rate of firing* Will cause firing immediately after the end of the absolute refractory period * producing the the highest possible rate of firing*
What does the speed of regeneration action potential depend on?
Capacitance current flow
What is one way to increase conduction velocity? How can we do this?
Decrease the axial resistance of the axon We can do this by increasing the diameter of the axon *large diameter = fast conduction velocity*
What other cells can generate an action potential?
Excitable cells: such as skeletal, cardiac, and some types of smooth muscle
What do compounds that interfere with normal sodium channel function cause? List 5
Failure of action potential generation, with potentially fatal consequences. 1. Tetrodotoxin 2. Saxitoxin 3. Local anesthetic like procaine and lidocaine 4. Antiarrhythmics 5. Antiepileptic durgs 6. Other toxins such as batrachotoxin
Describe the voltage sensor in the voltage gated sodium channels. What does it do? At normal, where is the sensor?
High concentration of + aa Mobile within channel structure Bc it is charged and mobile, The position of the sensor depends on the charge distribution across the membrane Normal = negative resting membrane potential therefore the charge distributed across the membrane holds the voltage-sensor at an inward (closed) position
Neurons what happens after the action potential?
Hyperpolarizing afterpotential or undershoot, where the membrane potential becomes more negative than at rest
What is the voltage dependent potassium channel distribution in myelinated axon's?
Increase in potassium channel density in the nodes and the juxtaparanodal region of the axon
What does myelination do to membrane resistance? How?
Increases membrane resistance Myelin wrappings cover over any ion channels present in the membrane between nodes Thus increases length constant therefore: *capacitive current flows much further along a myelinated axon then on myelinated axon*
How do you action potential's propagate in myelinated axon's? What is this called?
Jump rapidly from one node of Ranvier to the next Saltatory conduction (means to dance or leap in Latin)
For unmyelinated axons what is the principal determinate of conduction velocity?
Length constant of the axon The longer length constant = higher capacitive current from an action potential at one segment to flow further along the axon axon THUS: this allows the action potential to be regenerated at greater distances along the axon THUS: increasing the rate of the action potential propagation
What does myelination do to membrane capacitance? How? Why is this good?
Membrane capacitance is decreased This is because myelination increases the effective plasma membrane thickness *this offsets the increase in membrane resistance so myelination is a very efficient mechanism for increasing conduction velocity since length constant increases without a corresponding increase in time constant*
What happens to membrane potential during the fall phase/after?
Membrane potential will become more negative than at rest
What are antiarrhythmics?
Mexilletine, procainamide, lidocaine (also used as a local anesthetic) Partially block cardiac voltage sodium channels and can help control arrhythmias of the heart
Do all potassium channels close after the following phase of the action potential is completed?
No, some of these channels remain open even after the following phase of the action potential is completed. The total membrane potassium permeability is higher than normal for several milliseconds after.
Describe the process of channel activation, what happens to the port, the voltage sensor, and the ball and chain? (3)
Occurs when the depolarization of the membrane to the threshold level redistributes charge and weakens the force holding the sensor inward. Thus, the voltage sensor shifts outward and the channel pore is opened, allowing sodium current to flow into the cell At this point ball and chain is exposed to binding site and briefly allows channel to remain open
When do delayed rectifier channels open? Why? What does this do?
Open during action potential Actually have current flowing at herring falling phase of action potential Gated by membrane depolarization and open more slowly than sodium channels, so they do not begin to open until near the peak of activation potential. This allows the rate at which potassium ions to flow out of the cell to increase which hyperpolarizes cell.
What are action potentials that propagate in a normal direction (only one way)
Orthodromic
What are antiepileptic drugs?
Phenytoin, lamotrigine, and carbamazepine Drugs that control seizures act on voltage gated sodium channels. The effects of these drugs on sodium channels are complex. The principal effect is to promote the in activated or refractory state of the channel, reducing the ability of neurons to fire action potential's at a high rate.
What are other toxins such as What are other toxins such as Batrachotoxin?
Poison from South American poison dart frogs. Some sea anatomy and scorpion toxins. Plant toxins aconitine and veratridine These toxins alter activation and in activation of voltage gated sodium channels, thereby interfering with normal action potential initiation
What is Saxitoxin (STX)?
Produce by marine dinoflagellates. Responsible for "red tide" Blocks voltage gated sodium channels Shellfish and other marine organisms can be contaminated by these dinoflagellates. Ingestion of contaminated shellfish causes paralytic shellfish poisoning, which can be fatal.
What determines the maximum firing rate of action potentials?
The absolute refractory period because it defines the minimal interval between consecutive action potentials
What portion of the neuron generates action potential's? Why is this?
The axon membrane This is because voltage gated sodium channels are NOT distributed evenly throughout the neuron membrane. And a higher concentration of sodium channels are found in the axon rather than other areas of the neuron
What happens when there is a sustained depolarizing current?
The cell membrane potential stays positive to threshold and typically causes repetitive firing of action potentials
What occurs in sodium channel inactivation?
The channel is rapidly closed off by the "ball"
What is capacitive current? What does it do?
The current flowing down the axon ahead of the action potential. It alters the charge stored on the membrane's capacitance
What is an action potential?
The flow of a large enough inward current to depolarize to a critical level, causing the membrane potential to abruptly change from negatvie to positive and then back to normal. *The rapid, brief + membrane potential is the action potential*
Which conducts velocity faster, a myelinated axon or an on myelinated axon? Let us say they are the same size in diameter
The myelinated axon
What is relative refractory period? What causes this?
The period of time when it is possible for a second action potential to be generated, but the amount of current required to deep polarized the membrane to the threshold is greater Caused by the slow closing of delayed rectifier potassium channels, with residual inactivation of some voltage gated sodium channels also contributing
When the voltage sensor is closed what is the pore?
The pore is closed (due to voltage sensor being inward
What happens once all the voltage gated sodium channels are open?
The ratio of K+ : Na+ changes from 20:1 to about 1:20 (At the peak of the action potential)
What is frequency coding?
The relationship between the magnitude of sustained deep polarization (which depends on stimulus intensity) and the rate of action potential generation
What are local anesthetics such as procaine, lidocaine etc.
These drugs are derivatives of cocaine and are used as local anesthetics. They act by blocking voltage gated sodium channels.
What do compounds that affect voltage potassium channels cause? List three
These toxins block delayed rectifier potassium channels, increasing the duration of the action potential in shortening the refractory period. *Poisoning may lead to conversions, because these changes enhance action potential initiation* 1. Tetraethylammonium 2. 4-aminopyridinde 3. Some ions (barium, cesium)
Knowing what you know about myelination, what do you think demyelinating disease is do?
They slow or halt action potential propagation along affected axons
How long do the voltage gated sodium channels keep this large increase in sodium permeability during action potential? Why? What happens after?
Very brief, they are rapidly in activated through the ball and chain mechanism. Once the sodium channels become an activated the original resting membrane potential will be restored
What is the voltage dependent sodium channel distribution in myelinated axon's?
Voltage dependent sodium channels are densely clustered in axons within the nodes of Ranvier (since these channels are needed for generating an action potential, the current which generates action potential's flows only across stretches of axon membrane's within the node) The density of sodium channels in the internodal membrane is very low
In the neuron membrane which channels are at a higher concentration, K+ or Na+?
Voltage gated Na+ channel is greatly outnumber leak K+ channels
How are the intensity of sensory stimulation and the rate of action potential firing related?
When the intensity of sensory stimulation increases, the rate of action potential firing also increases
