What are the three fundamental characteristics of a channel?
whether or not it can be inactivated
What are the three ways channels can be gated?
What is a rectifier?
A rectifier basically is what returns the system to the resting potential
so if the membrane is depolarized, the rectifier will repolarize it
if the membrane is hyperpolarize it, it will depolarize back to the RMP
K+ channels are often rectifiers
WHat channels establish the RMP?
the leak channels - the ones that are open at rest
voltage gates channels have __ subunits and ligand gated channels have __ subunits.
voltage = 4
ligand = 5
Which leak channels are primarily resonsible for the RMP in a neuron?
open K+ leak channels
some Na+, but mostly K+
In a neuron, which type of channel can be inactivated, Na+ or K+?
that's why there's an overshoot hyperpolarization at the end of an action potential - the K+ channels can't be inactivated, so it takes longer for them to close,
At what membrane potential will an ion stop flowing in either direction?
At the reveral potential (or equilibrium potential) for that specific ion.
this is essentially when the chemical and electrical forces are in balance
calculated by the Nernst equation
What is the Erev for Na+, K+, and Cl-?
Na+ = 60 mV
K+ = -88 mV
Cl- = -61 mV
What is the average RMP in a neuron?
about -70 mV relative to the outside of the membrane
Besides the resting membrane potential, what are the other two types of potentials?
In which type of potential is the amplitude of the change proportion to the magnitude of the input?
Graded potentials (higher input, higher membrane change)
Action potentials are all or none
True or false, graded potentials can only be depolarizing.
graded potentials can either be depolarizing or hyperpolarizing
unlike action potentials, which are always depolarizing at first, followed by a hyperpolarization
What is the cell's resistance based on?
How does resistance related to voltage change?
the resistance is based on the number of open channels = more open channels = less resistance
the higher the resistance, the greater the voltage change will be (V = IR)
True or false:
THe more channels that are open, the greater the voltage change across the membrane will be.
It goes back to resistance.
Fewer channels open = greater resistance = greater voltage change
What does it mean to say that graded potentials are passive?
they will travel equally in all directions and decrease in amplitude with distance
What are the 3 types of graded potentials
1. post-synaptic potentials - in neurons (EPSPs and IPSPs)
2. End plate potentials in muscle cells
3. receptor potentials in sensory systems
What is the length constant?
an expression of how far a graded potential can be transmitted along a membrane
it's equal to the distance where the amplitude has decayed to 37% of the original amplitude
What affects the length constant, in what way?
1. membrane resistance: higher resistance, higher the length constant
2. axial resistance (the diameter of the axon): higher diameter, lower resistance, higher the length constant
Neuronal regions with high membrane resistance and low axial resistance (myelinated asons) have ____ length constans, so they can transmit potential changes over ___ distances
long length constants
What is the temporal and spatial relationship between graded potentials and action potentials?
the graded potentials occur first. If they can depolarize the membrane to threshold (-40 mV), they will trigger an action potential that will travel further down the axon
what channels are opened at threshold?
the voltage gated Na+ channels, so Na+ floods into the cell, causing rapid depolarization
As the Na+ channels start to be inactivated, what open?
the voltage gated K+ channels (the delayed channels)
what is threshold in a neuron?
usually -40 mV
true or false: once initiated, all action potentials will be identical.
false - they can be different shapes and sizes depending on what channels and neurotransmitters are involved
In general, which channels areresponsible for depolarization and which are responsible for repolarization?
Na+ is depolarization
K+ is repolarizing (and hyperpolarizing)
Why does the action potential peak at +40 mV and not +60 mV, which is the Erev for Na+? 4 reasons...
1. the Na+ channels become inactivated
2. As Na+ enters the cell, you get a decrease in the electrical driving force for more Na+ to enter, so it slows down
3. Cl- channels become involved as the membrane potential leaves -06 mV, so Cl- will move into the cell and play a role in the hyperpolarization
4. the rectifier VG K+ channels open and K+ leaves the cell, causiong hyperpolarization
At what point do the Na+ channels go back from inactivated to closed?
during the relative refractory period - as the K+ channels are closing
Why is hyperkalemia such an issue?
If there's too much extracellular K+, the E rev and Vm of K+ changes and the VG K+ channels won't close again - this means you won't be able to fire anymore action potentials - the RMP will be too hyperpolarized.
What does poisoning with tetrodotoxin, saxitosin and brevitoxin do?
They block the VG Na+ channels so that you don't get action potentials in the nerves going to the lungs and you die from respiratory depression
What is hyperkalemic periodic paralysis?
It's an autosomal dominant mutation in muscle VG Na+ channels, such that they get less Na+ entering their cells during exercise and the muscles can't fire = paralysis
In what state are the VG Na+ channels during the absolute refractory period?
the majority of the Na+ channels are inactivated
this means that the cell membrane cannot immediately produce a second AP
In what state are the VG Na+ channels during the relative refractory period?
they are transitioning baack from the inactivated to the closed state
in other words, they become capable of opening again
this menas it's possible to have another action potential, but it takes a greater stimulus to do so
True or false, the action potential fired during the relative refractory period will be the same as the first.
False - it will be smaller
Why is the propagation of an action potential unidirectional?
the absolute refractory period prevents the initiation of an AP in the region of membrane that has just produce one (can't go backwards).
How does AP propagation occur in myelinated axons?
its through saltatory conduction...
depolarization only occurs at the nodes
the signal propagates down the axon under the myelin (higher resistance = longer length constant) and triggers the sodium channels to open at the node, causing depolarization
then it jumps to the next node
What two things determine the conduction velocity of nerve fibers?
the diameter and degree of myelination
more myelination = faster
greater diameter = faster
WHat are the subcategories of nerve fibers arranged from fastest conduciton to slowest conduction?
A-alpha (motor neurons)
A-beta (sensory neurons)
A-gamma (sensory neurons)
B (autonomic nervous system)
What are the two types of synapses?
chemical and electrica
What are the properties of an electrical synapse?
1. it's the passage of a graded potential from one cell to another
2. they're passive, so the signal will decay with distance
3. they'll be extremely rapid
4 will be bidirectional
What are the properties of chemical synapses?
1. similarly to an AP, a weak signal can be transferred in an all-or-none way
2. slower because of synaptic delay
3. use NTs
4. unidirectional (pre to post synaptic)
What are the 3 fundamental steps in chemical neurotransmission?
1. NT release
2. receptor activation
3. NT inactivation
How often does a synapse actually fire an action potential when it's signalled to?
It depends on the tissue, but electrical and chemical synapses in the brain actually fail about 50% of the time!
WHat are the steps in neurotransmitter release coupling?
1. depolarization reaches the terminal membrane
2. activation of voltage gated Ca2+ channels
3. Ca2+ enters the cell
4. Ca2+ causes a conformational change in the docking proteins
5. The vesicles fuse to the plasma membrane
6. NT is released into the synaptic cleft
the amount of Ca2+ that enters the cell depends on what?
the size and shape of the action potential
If you _____ the terminal membrane, you will de-inactivate the VG Ca2+ channels, making them more likely to ____ if threshold is reached, and therefmore making it ____ likely NTs will be released.
If you hyperpolarize the membrane, you'll be de-inactivating the VG Ca2+ channels, making them more likely to open if threhold is reached, and therefore making it more likely NTs will be released
What happens in Lambert-Eton Syndrome?
It's an autoimmune disorder that attacks some VG Ca2+ channels in the periphery
this means you get less Ca2+ triggered NT release in the periphery
this manifests in muscle weakness that will go away the more you try to contract the muscle (because the Ca2+ will eventually build up- it just takes longer)
What is the treatment for Lambert-Eton Syndrome?
It's a K+ channel blocker that serves to prolong the action potential and therefore increase the liklihood that the Ca2+ channels will open to allows Ca2+ to enter the cell and trigger NT release
WHat does botox do?
It destroyes the docking proteins in cholinergic nerves
this means you don't get NT release and thus muscle contraction is decreased = less wrinkles, less twitches
What does tetanus \do?
it's retrogradely transported back to inhibitory nerves
it dcreases the inhibitory nerve's ability to send inhibitory signals and thus you get an INCREASE in muscle contraction
What is a quantum?
1 quantum = the amount of NT held in 1 vesicle
What does Dale's prinicple say?
In general, all axonal branches of a neuron release the same NT substances from each nerve terminal.
What are some of the NT and substances that can be released from nerve terminals?
- it will release the primary NT
- then it will release neuromodulators that influence the action of the primary NT
classic NTs: ACh, NE, GABA, 5HT, glutamate, glycine, ATP
peptides: endorphins, insulin, enkaphalins
Receptor mecanisms can be classified in what two ways?
Speed (fast or slow) and action (excitatory or inhibitory)
What is the difference between an ionotropic receptor and a metabortropic receptor?
An ionotropic receptor itself is the ion channel, so its action is very fast
A metabotropic receptor involves a 2nd messenger to act as the ligand to open the ion channels, so it's slower
What are the 5 ionotropic receptors that cause excitatory signals?
What are the two inhibitory ionotropic receptors we talked about?
What do agaonists do?
What do antagonists do?
Agonists will bind tot he active site and produce the same effect as the native NT
An antagonis will bind the active site and have NO effect, thus preventing the effect of the native NT
What type of receptor is the nicotinic receptor?
it's a 5-subunit ligand gated receptor (Ach) that, when open, acts as a nonselective cation channel that allows K+, Na+ and Ca2+ to go through
At rest, if the nictoinic receptor opens, which ion is more likely to flow through the fastest and why?
the Na+ because at the resting membrane potential of -70 mV, Na+ is the ion that is furthest away from its Erev (+60 mv), so it will flow through the fastest and you'll get Na+ entry/depolarization
As Na+ rushes into the cell through the nicotnic receptor, what will happen as it depolarizes?
the membrane potential will get further away from the Erev for K+ (-88 mv), so K+ will begin to exit the cell, meaning the EPSPs will be self-limiting (and won't reach the Erev of Na+)
What happens in myasthenia gravis?
it's an autoimmune disease against he nicotinic ACh receptors
patients get rapid muscle fatigue because the nicotinic receptors won't open for the ions to enter = no EPSPs
What is the treatment for myasthenia gravis?
give an acetylcholinesterase inhibitor to block the degradation of ACh
What are thet wo glutaminergic receptors we talked about?
the AMPA and NMDA
Describe the AMPA channel.
It's a non-selective cation channel
when opened at rest, Na+ will enter the cell first, then K+ will leave
it will open and close quickly due to desentitization
Describe the NMDA receptor. WHy is it unique?
The NMDA receptor is unique in that it is both voltage AND ligand gated
1. At rest, the receptor is blocked by MG2+, so even if it opens, no ions will go through at the restine membrane potential
2. WHen the membrane depolarizes (through AMPA usually), the inside becomes more negative and the Mg2+ is pushed out
3. when glutamate binds without Mg2+ inside, the channel will open and the cations will be able to flow (Na+ and Ca2+ in and K+ out)
WHy is the NMDA receptor considered activaty dependent activation?
it takes depolarization to get more depolarization
the Na+ influx keeps the channels open in a positive feedback loop.
WHat role does Ca2+ play in the NMDA receptor?
it will enter the cell when the receptor is open and you get calcium induced calcium release, which alters channel function
What HUGELY IMPORTANT role does the NMDA receptor play?
It's the underlying cause of learning and memory because it's pivitol in long term potantial and changing gene expression with anatomical remodeling
Describe the GABA receptors
they are the predominant inhibitory receptor in the brain
it's a chloride channel that produces inhibition by basically stabilizing the RMP around -61 mV
If the membrane is hyperpolarized, the Cl- will leave the cell, bringing it back to RMP
If the membrane is depolarized, the Cl- will enter the cell, bringing it back to RMP
What are the 3 mechanisms for NT inactivation?
1. diffusion (glutamate and GABA)
2. enzymatic degradation (ACh)
3. Reuptake (monoamines and 5HT)
What breaks down ACh?
acetylcholinesterase in the synaptic cleft
Individual ESPs are generally too small to trigger an AP, so what has to happen?
synaptic summation or integration
What are the two types of synaptic summation?
1. temporal summation - summate the output of a single (or multiple) pre-synaptic neuron EPSPs that are occuring in quick temporal succession)
2. Spatial summation - integrate the EPSPs from multiple pre-synaptic neurons on the same post-synaptic neuron