Action Potentials and Graded Potentials

What is the body plan of the voltage-gated sodium channel?

-6 transmembrane (TM) segments/subunit or motif, 4 subunits or motifs/channel.

Once the threshold potential has been reached, what happens?

-A class of channels known as voltage-gated Na+ channels open -These channels only open when the threshold potential has been reached (-40 mV), and they all open at the same time -Their channel density is highest at the axon hillock is huge

Variable Amplitude of graded potentials

-A graded potential can make the resting membrane potential either less negative (depolarization) or more negative (hyperpolarization)

Action Potential Propagation

-A graded potential of a low amplitude (subthreshold) is not going to reach the action potential threshold -As you increase the size of the stimuli an the amplitude of the corresponding graded potential, eventually you will cross the threshold potential

For stimulus intensity to be conveyed, what happens?

-A greater stimulus intensity will, in general, generate more than one AP - transduce it in terms of AP frequency

How many genes encode the voltage-gated sodium channel?

-A single gene

What is the absolute refractory period?

-Absolute refractory period: a second action potential cannot occur when Na+ channels are open or in the inactivated state

What is saltatory conduction?

-Action potentials occur at the nodes of Ranvier, where voltage-gated Na+ channels are concentrated (~1000 per µm2). -Action potentials "jump" from one node to the next

Action Potentials: Sequence of AP generation Step 6

-After hyperpolarization -Afterhyperpolarization occurs because voltage-gated K+ channels close relatively slowly, allowing more time for K+ to leave the cell

What are the functions of the absolute refractory period?

-Allows re-establishment of the resting membrane potential -Directs the action potential towards the nerve terminal -Limits #APs in a given period -Separates APs, allowing passage of individual signals

During an action potential, voltage-gated calcium channels are also activated. What do they do?

-At -20 or -30 mV, voltage-gated Ca channels opne -Allowing calcium to rush into the cell -One of the things that it does is it opens Ca-activated Potassium channels -After a series of APs, enough Ca comes into the neuron to activate the Ca-activated Potassium channels- this causes the slow after hyperpolarization- that follows a whole string of APs caused by a very strong stimulus

What is the structure/function of the voltage-gated sodium channel?

-Beta hairpin between TM5-6 lines the pore (arrows in top figure) and is likely part of the selectivity filter, amphipathic charged TM4 (yellow) is the voltage sensor S4 -The inactivating particle is actually an intracellular amino acid loop

Some symptoms of demyelinating diseases

-Blurriness in the central visual field that affects only one eye; double vision -"Odd" sensation in legs, arms, chest, or face, such as tingling or numbness (neuropathy); -Weakness of arms or legs; -Cognitive disruption including speech impairment, memory loss -Heat sensitivity (symptoms worsen, reappear upon exposure to heat such as a hot shower); -Loss of dexterity; -Difficulty coordinating movement or balance disorder; -Difficulty controlling bowel movements or urination; Fatigue

Calcium entering the cell slows down the frequency of APs. Why?

-Calcium is building up within the cell after each AP and its activating potassium channels- which are brining the membrane back towards RMP

What are the kinds of graded potentials?

-Can be either depolarizing or hyperpolarizing

Where do graded potentials flow?

-Change in potential flows to adjacent membrane regions

Decremental potential spread: The Nerve Cell Membrane is an RC Circuit What is the role of the ion channels?

-Channels allow or limit ion flow -Channels act like a resistor -Resistance is dependent on the number of channels -Conductance is equal to the inverse of resistance

Graded Potential- Initiation 1st Step

-Chemical signal (ligand) binds to a gated channel prompting it open

Where do graded potentials operate?

-Confined to relatively small region of membrane

Action Potentials: Sequence of AP generation Step 4

-Depolarization stopped by inactivation of Na+ channels and opening of K+ channels

All receptor potential are depolarizing or hyperpolarzing? What about synaptic potentials?

-Depolarizing -Synaptic potentials can be either

What is the Length/Space Constant?

-Determines how far a charge will spread before it decays -Equal to (Transmembrane resistance (Rm)/Axial (internal/longitudinal) resistance (Ri))

Why do APs only travel in one direction?

-Due to the absolute refractory period

What does it mean for action potentials to be "all-or-none"?

-Even if you increase the size of the stimulus, it does not matter. The extent to which an Action potential depolarizes will always be the same. -they either occur maximally or they do not occur at all

How are graded potentials usually initiated?

-From some sort of outside stimulus, be it environmental or a neurotransmitter

What types of channels mediate graded potentials?

-Gated channels- opened by some sort of stimulus, i.e., mechanical, chemical, etc.

Where do the action potentials initially propagate?

-In the axon hillock -It is loaded with voltage-gated Na channels -They transduce that information not in terms of voltage change but by frequency of APs (number of APs)

Graded Potential- Initiation 2nd Step

-Ions being to flow through the open channel at the section of the cell membrane -In this case, it is a sodium channel, so there is a local depolarization

Graded Potential- Initiation 3rd Step

-Ions move across the membrane and change the charge -It is the charges, not the ions, that have to discharge- so it dissipates along the membrane in all directions -The movement of the charge is not the same as the movement of the ions- governed by electrical principles -Once the charge has entered, there is immediate discharge

What happens to the Length Constant if you increase membrane resistance (Rm)?

-It will lengthen -Green line on the diagram

What happens to the Length Constant if you increase axial resistance (Ri)?

-It will shorten -Red line on the diagram

How would the time constant change with increased channel density?

-It would shorten -Channels=Resistors- and conductance is equal to 1/R -Blue line on the diagram

Why do graded potentials experience decremental conduction?

-Leakage of charge (mostly K+): like water flowing through a leaky hose: less water flows the farther from the faucet

How would the time constant change with increased capacitance?

-Lengthen -Increased via increasing surface area -Red line on the diagram

Why are graded potentials decremental?

-Magnitude of potential decreases with increasing distance from point of origin and time

Action Potentials: Sequence of AP generation Step 1

-Neuron is at RMP

Action Potentials: Sequence of AP generation Step 3

-Positive feedback loop allows rapid entry of Na+, rapid depolarization, bringing membrane closer to ENa (+60 mv)

What is the function of the relative refractory period?

-Provides control over the frequency of action potentials

What is the Length/Space Constant?

-Regarded as the distance it takes for any graded potential to return to 63% of it's maximal level

What is the membrane time constant?

-Regarded as the time it takes for any graded potential to return to 63% of it's maximal level

Action Potentials: Sequence of AP generation Step 5

-Repolarization, bringing membrane closer to EK (-90 mv)

What determines the time course of membrane potential changes?

-Resistance and Capacitance

Action Potentials: Sequence of AP generation Step 7

-Return to resting membrane potential

Channelopathies can contribute to what?

-Seizures

When the voltage-gated Na+ channels open up, what happens?

-Sodium rushes into the cell, and their is a massive depolarization

Graded Potential- Initiation 4th Step

-The area of depolarization is limited to the site of the stimulus and the area where the discharge occurs -However, that initial discharge spreads passively across the membrane in all directions

Decremental potential spread: The Nerve Cell Membrane is an RC Circuit The larger the membrane surface area what is seen in regards to the change in capacitance?

-The greater the capacitance

At the onset of the action potential, what happens to the membrane sodium permeability for sodium?

-The permeability for sodium goes way up ( 20) (potassium remains the same (1))

Decremental potential spread: The Nerve Cell Membrane is an RC Circuit What is the role of the membrane itself?

-The plasma membrane acts a capacitor -The opposing charges line up right along the membrane, and they build up- resulting in the formation of a capacitor -All you need is for a channel to open to allow the dissipation of that stored energy across the membrane

Decremental potential spread: The Nerve Cell Membrane is an RC Circuit How do you get the change in membrane potential?

-The propagated graded potential has to discharge the capacitor, and that discharge must travel through a resistor (ion channel) -The number of channels affects how much current is flowing through any given point in a membrane -Together Resistance and Capacitance determine the time course of membrane potential changes.

Variable Amplitude of graded potentials

-The size of a graded potential is proportional to stimulus intensity (this is the basis for the word "graded")

What does the term "graded" mean?

-The voltage change is dependent upon the size of the input, whatever it might be

Why does the action potential usually top off at roughly +30 mV and never reaches the equilibrium potential of sodium (+60 mV)?

-The voltage-gated Na+ channels have an inactivation gate- which blocks the open channel almost immediately after it opens- this limits the flux of Na+ ions

After a AP, what produces the transient hyperpolarization?

-The voltage-gated potassium are slow to close resulting in the hyperpolarization

Action Potentials: Change in ion permeability Potassium

-The voltage-gated potassium channels have varying degrees of activation- open at different membrane potentials- membrane potential has to be heading towards 0 before they open though -When they do open, potassium rushes out of the cell, bringing the membrane potential back down to RMP levels

What happens after the threshold potential has been reached?

-There is a huge spike in voltage across the membrane thanks to the influx of sodium into the cell (depolarization)- goes to around +20 or +30 mV

Graded Potentials vs. Action Potentials

-They are BOTH mediated by changes in membrane permeability (opening or closing of ion channels) -When channels open, ions flow across the membrane- which causes a current -This results in a transient change in membrane potential -This is how neurons communicate with each other

Graded Potentials - Conducted decrementally

-They have the highest intensity closest to the site of the initial stimulus, and that intensity decreases the farther away you are from that initial site

What other types of channels open up when threshold potential has been reached?

-Voltage-gated K+ channels -Open and close more slowly than the sodium channels

Action Potentials: Change in ion permeability Sodium

-Voltage-gated sodium channels open up as soon as the threshold potential is reached, causing the cell to depolarize -As soon as they open though, the inactivation gate blocks the channel -As soon as RMP is reached though, the inactivation gate is removed, and the channel fully closes

Where do graded potentials tend to transmit info?

-Within a neuron -(e.g., synaptic potentials)

Decremental potential spread: The Nerve Cell Membrane is an RC Circuit So as you open up more and more channels, what happens?

-You increase conductance and decrease resistance

What is the relative refractory period?

-a second action potential can occur during after hyperpolarization, but only if the stimulus is strong enough

What are action potentials?

-are large-scale, all-or-none, local changes in membrane potential that propagate long distances, huge voltage changes

What are graded potentials?

-are small-scale, variable amplitude, local changes in membrane potential that degrade over distance from initiation site -They spread out across the membrane and degrade over time (without the initial input) -Larger input will result in a larger graded potential -(e.g., receptor potentials, synaptic potentials)

Genetics behind the voltage-gated potassium channels

-for K channels a gene encodes 1 of 4 subunits, which then assemble to form a functional channel

Because of this "all-or-none" nature, a single AP cannot convey?

-information about stimulus intensity

What does tetrodotoxin do?

-is an extremely potent toxin in ovaries of puffer fish (fugu, a delicacy in Japan) that specifically binds to Na+ channels and prevents APs -Can cause rapid death

What is the membrane time constant?

-is an index of how rapidly potential can change -is equal to Resistance X Capacitance

What are the symptoms of tetrodotoxin poisoning?

-paresthesia of lips and tongue; paresthesia of face and extremities, hypersalivation, incoordination; severe nausea, diarrhea, abdominal pain; paralysis, cardiac arrhythmia; respiratory failure; death.

What does procaine (novocaine) and lidocaine block?

-partially block voltage-gated Na+ channels, preventing them from opening. -This prevents sensory nerves from transmitting pain signals.

Action Potentials: Sequence of AP generation Step 2

-stimulus results in a graded potential which results in the crossing of the threshold potential

Where do action potentials tend to transmit info?

-transmit information for communication between neurons (release of neurotransmitters from the axon terminal)

Characteristics of Voltage-gated sodium channels

1.) Fast opening 2.) Fast closing 3.) Inactivate spontaneously

Characteristics of Voltage-gated potassium channels

1.) Slow opening 2.) Slow closing 3.) Only inactivate when membrane repolarizes

What does myelination do to the conduction of APs?

Myelination dramatically increases the speed and fidelity of AP propagation because: -Myelin (made by oligodendrocytes or Schwann cells) is an insulator that reduces leakage of current across the membrane, so the path of least resistance for a local current is at the next node -Concentration of voltage-gated Na+ channels is low in myelinated regions, thus also reducing leakage of current.