Neuronal Function Flashcards
What major system is involved in neuronal function
the nervous system
What are the main functions of the nervous system?
perception
learning and memory
decision making
sensing environment
motor signal delivery
Where are communication and information processing encoded?
in neuron activity and chemical signaling
What are the 2 parts of the nervous system?
central nervous system (CNS)
peripheral nervous system (PNS)
What are the components of the CNS?
the brain and spinal cord
What are the components of the PNS?
neurons and glia external to the CNS
T or F: neurons and glia are only found outside the CNS
false, they are also present in the CNS
What allows a large complexity of behaviours in humans?
the massive amount of neurons and synapses in our brains
What happens in the signal reception neural zone?
dendrites and cell body receive incoming signal and convert it into a change in membrane potential
How many neurons are in the human brain? How many synapses?
neurons: 10^11
synapses: 10^14-10^15
T or F: all neurons have the same structure and properties
false
T or F: all neurons use the same basic mechanisms to send signals
true
What are the 4 basic neural zones of a motor neuron?
signal reception:
- dendrites
- cell body (soma)
signal integration:
- axon initial segment
signal conduction:
- axon (some in myelin sheath)
signal transmission:
- axon terminals at the synapse
What happens in the signal integration neural zone?
at the axon initial segment, a signal (change in membrane potential) is converted into an action potential
What happens in the signal conduction neural zone?
the axon potential travels down the axon (sometimes covered in a myelin sheath)
What happens in the signal transmission neural zone?
the action potential reaches the axon terminals (presynaptic boutons) and causes the release of a neurotransmitter into the synapse
Where in a neuron is an action potential generated?
in axon initial segment where the membrane potential change is converted into an action potential
What are dendrites? What is their function?
fine, branching extensions projecting from the neuronal cell body
dendrites sense incoming signals and convert them into electrical signals by changing the membrane potential which is transmitted to the cell body
What is the cell body? what are its functions?
stores the nucleus, most organelles, and is the location of protein synthesis
functions in receiving incoming signals
What is the axon hillock? what are its functions?
the axon hillock is involved in signal integration
its located at the junction between the cell body and the axon
this is where an action potential can be generated
- if an incoming signal sent from the dendrites and cell body is large enough when it reaches the axon hillock, an action potential will occur in the axon
What is the axon? what are its functions?
extending from the axon hillock and cell body, a skinny extension is where the action potential is initiated if the signal at the axon hillock is large enough
What part of the neuron is specialized for signal conduction?
the axon
T or F: axons are usually really short, but some can be multiple meters long
true, most are only a few mm long but for ex. in blue whales, axons are 25m long
What is a myelin sheath? what is its function? what type of neurons have these?
a coating of Schwann cells that intermittently wrap axons of vertebrate motor neurons to increase the conduction speed of electrical signals to axon terminals
What are axon terminals? what are their functions?
specialize in signal transmission to target cells
axons usually have multiple axon terminal branches
converts the electrical signal (action potential) into a chemical signal (neurotransmitter)
What is the main property of neurons that allows them to store, recall, and distribute information?
their excitability (ability to alter their membrane potential rapidly)
What acts as an electrical signal for neurons?
changes in a neuron’s membrane potential
What do the axon terminals of one neuron form with the target cell?
a synapse
T or F: neurons are the only cells specialized to use changes in membrane potential as an electrical signal across long distances
true
What occurs at the synapse?
the synapse is the junction between a motor neuron’s axon terminal and a target cell
the action potential is converted into a chemical signal (neurotransmitter) at the axon terminal and is released into the synapse where it diffuses to receptors on the target cell
What is a resting membrane potential/when does this occur?
the voltage difference (mV) of a neuron’s membrane when the cell is not sending an electrical signal (at rest)
What is the most common resting membrane potential (Vm) for neurons? what does this mean in relation to the internal and external cell environment
-70 mV
the inside of the cell membrane is 70mV more negative than the outside of the membrane
it’s expressed relative to the external voltage
What 3 ways can a neuron change its membrane potential?
depolarization
repolarization
hyperpolarization
Define depolarization
when the membrane potential becomes more positive than resting
Define repolarization
when the membrane potential returns to resting potential
Define hyperpolarization
when the membrane potential becomes more negative than resting
What determines the membrane potential/establishes the potential difference across a membrane?
the relative permeabilities of the membrane to specific ions and the concentration gradients of those ions
How are the concentration gradients of ions influenced when the membrane potential is resting?
there’s no net ion movement across the membrane because the RMP counteracts the chemical gradients
What is an equilibrium potential for an ion?
the membrane potential at which an ion is distributed equally across a membrane
ex.
K+ inside cell high, K+ outside cell low
K+ leaves cell along chemical gradient, but this makes inside the cell more negative, so the electrical difference brings more K+ ions back in
eventually the driving force pushing K+ out the cell and the electrical force bringing K+ back into the cell balance out = the membrane potential here is the equilibrium potential
What is the Nernst equation used for?
calculating the equilibrium potential for an ion
What is the Nernst equation?
Eion = (RT/zF) ln ([X outside] / [X inside]
where:
R is the gas constant (8.31 joules/moleK)
T is temperature in K
z is the valence of the ion
F is the Faraday constant (96,485 joules/Voltmol)
[X] is the concentration (M) of the ion
units need to be converted from volts into mV
Explain what it means for K+ to have an equilibrium potential of -60mV?
the driving force that moves K+ out of the cell (chemical gradient) is balanced by an additional 60mV of negative charge inside the membrane
so membrane potential has to be hyperpolarized by 60mV to balance the chemical gradient of K+
What is the reversal potential?
Also the equilibrium potential of an ion because the direction of the ion movement is reversed when the equilibrium potential is reached
Use the Nernst equation to calculate the equilibrium potential for K+ when:
20 degrees C
intracellular K+ = 140 mM
extracellular K+ = 2.5 mM
should equal -101 mV
Use the Nernst equation to calculate the equilibrium potential for Na+ when:
20 degrees C
intracellular Na+ = 10 mM
extracellular Na+ = 120 mM
should be +63 mV
Use the Nernst equation to calculate the equilibrium potential for Cl- when:
20 degrees C
intracellular Cl- = 1.5 mM
extracellular Cl- = 77.5 mM
should be -99 mV
What’s the z value for K+?
valence of K+ = +1
What’s the z value for Na+?
valence of Na+ = +1
What’s the z value for Cl-?
valence of Cl- = -1
why are Na+, K+, and Cl- important ions to understand their equilibrium potential?
because all 3 have leak channels in a neuron membrane and contribute to the changes in the membrane potential
What factors contribute to membrane potential?
distribution of ions across membrane
relative permeability of the ions controlled by leak channels
charges of the ions
How is the membrane potential calculated?
the Goldman-Hodgkin-Katz equation for Vm
what is the Goldman-Hodgkin-Katz equation for membrane potential?
Vm = (RT/F)ln* (Pk[K+out] + PNa[Na+out] + PCl[Cl-in]) / (PK[K+in] + PNa[Na+in] + PCl[Cl-out])
it’s the sum of the equilibrium potentials for the ions considered while considering the relative permeabilities of each ion (Pion)
What is g in the Goldman formula?
conductance which is similar to permeability
How can the Goldman equation be simplified?
by using g = conductance instead
Vm = (EKgK + ENagNa + ECl*gCl)/ (gK + gNa + gCl)
What two major ion pumps are involved in mediating membrane potential changes?
Na+ / K+ ATPase pump
How does the Na+ / K+ ATPase pump function?
it maintains the concentration gradient of Na+ and K+ across the membrane = maintains the membrane potential
for every ATP hydrolyzed:
3 Na+ ions pumped out cell
2 K+ ions pumped into the cell
For every ATP hydrolyzed, how many Na+ ions are pumped into or out of the cell?
3 Na+ out of the cell
For every ATP hydrolyzed, how many K+ ions are pumped into or out of the cell?
2 K+ ions into the cell
What does electrogenic mean?
a current is produced
What is the result of the Na+ / K+ ATPase pump?
it is electrogenic and produces a current
what is the major role of the Na+/K+ ATPase pump?
to maintain membrane potential by pumping the major contributors to membrane potential (Na+ and K+) across the membrane
Why do membranes have an intrinsic permeability to ions?
presence of leak channels
How does the membrane counteract the constant flow of ions along their chemical gradients?
the Na+ and K+ ATPase pump
T or F: neurons can alter the permeability of their membranes
true
why would neurons alter the permeability of their membranes?
to cause a change in their membrane potential to act as an electrical signal
How do neurons alter their membrane permeability?
by opening and closing certain ion channels
What happens to the charge difference during depolarization? What happens to the membrane potential?
the charge difference between the inside and outside of the cell membrane decreases = membrane potential becomes less negative
What causes depolarization of the membrane?
either positive ions entering the cell or negative ions leaving the cell will cause the membrane potential to become less negative
What happens to the charge difference during hyperpolarization? What happens to the membrane potential?
the difference between the inside and outside of the membrane increases and the membrane potential becomes more negative
What causes hyperpolarization of the membrane?
either negative ions enter the cell or positive ions move into the cell
When can repolarization occur?
either after a depolarization or hyperpolarization
What methods can be used to predict the direction of ion movement during signaling?
the Nernst and Goldman equations
Which ion channel opening causes the depolarization of the membrane?
Na+ channels open and the membrane potential becomes less negative and approaches the Na+ equilibrium potential
Which ion channel opening causes the hyperpolarization of the membrane?
K+ channels open and the membrane potential becomes more negative to reach the K+ equilibrium potential
Which direction does Na+ flow when the Na+ channels open?
Na+ flows into the cell to make the membrane potential less negative (depolarize)
which direction does K+ flow when the K+ channels open?
K+ flows out of the cell to make the membrane potential more negative (hyperpolarize)
What happens to the membrane potential as permeability to a specific ion increases? which equation predicts this?
membrane potential will approach that ion’s equilibrium potential
this is predicted by the Nernst equation
What are the voltage-gated channels?
Na+, K+, Ca2+
What are the ligand gated channels? what type of ligand is used?
glutamate receptors (NMDA, AMPA, kainate)
GABAa receptors, glycine recpetors
nicotinic acetylcholine receptors
5-HT3, P2X
ligands are neurotransmitters
What is conductance?
approximates permeability
the reciprocal of resistance
g= 1/resistance
What are graded potentials? What causes them?
changes to the membrane potential that vary depending on the stimulus intensity
caused by the opening and closing of ion channels
ex. a higher concentration of neurotransmitters increases the chances that an ion channel will open which results in more ion channels opening and staying open for longer = larger change to the membrane potential
What open ion channels will depolarize the membrane?
Na+ and Ca2+
what ion channels will hyperpolarize the membrane?
K+ and Cl-
T or F: graded potentials are long distance signals
false, they are short-distance - they degrade over time/distance
what is an electrotonic current spread?
when the positive charge from an influx of positive ions spreads along the membrane to cause depolarization
this is caused by positive charged ions attracting negative ones and repeling positive ones - pushing them along the membrane
T or F: depolarization strength remains constant as it spreads across the membrane
false, it decreases in strength
When a channel is closed, what is the membrane conductance and what is the resistance?
conductance is 0
infinite resistance
When a channel is open, what is the membrane conductance and what is the resistance?
the conductance will be a positive value and the resistance will be its inverse reciprocal
What is the electrochemical driving force? how is it expressed?
it’s how far the membrane potential is from the equilibrium potential of an ion - it determines if an ion will flow across the membrane
Vm - Eion
How is the current calculated?
I ion = gion (Vm - Eion)
What is the current?
the flow of ions per given time
what is voltage?
(V) is the difference in electrical potential
What is resistance?
the force opposing the flow of electrical current
What is Ohm’s Law?
Voltage (V) = current (I) * resistance (R)
What is capacitance? how is it calculated?
the ability of a membrane to store a charge (Q) when there’s a voltage difference between 2 surfaces
C = Q / V
What are 3 features of a capacitor?
- material properties of cell membrane
- area of 2 conducting surfaces (larger surface area = larger capacitance)
- thickness of insulating layer (greater thickness = lower capacitance)
How do neurons compensate for the fact that graded potentials (changes to the membrane potential) are short-distanced and degrading signals?
they convert the change to membrane potential to another electrical signal, the action potential
Which are longer distance signals: action potentials or changes to membrane potential?
action potentials
What triggers an action potential?
the net amount of graded potential at the axon hillock
What is the threshold potential?
the value that the membrane potential must reach in order to trigger an action potential (depolarized)
What is the most common threshold potential in neurons?
-55 mV
What amount of depolarization is required for an action potential to be triggered?
resting membrane potential is -70 mV
threshold potential is -55mV
so the membrane has to be depolarized by more than 15 mV to cause an action potential
what is a subthreshold potential?
a membrane potential that is not sufficient enough to cause an action potential
what is a suprathreshold potential?
a membrane potential that is above the threshold potential needed to initiate an action potential
what is an excitatory potential?
a depolarizing graded potential that brings the membrane potential at the axon hillock closer to the threshold potential
What is an inhibitory potential?
a hyperpolarizing graded potential that brings the membrane potential at the axon hillock farther from the threshold potential
What is the time constant (tau)?
the time it takes for the membrane potential to decay to 37% of its maximal value
basically it’s how well the membrane maintains its charge
What percentage is used to measure the time constant?
when the membrane potential decays to 37% of its maximum value
What variables affect the time constant?
cell membrane resistance
cell membrane capacitance
How is the time constant calculated?
tau = rm*cm
time constant = membrane resistance * membrane capacitance
If membrane resistance or capacitance is low, how is the time constant effected?
time constant is low
What are the consequences of a low time constant?
the membrane capacitor fills up faster
depolarization occurs faster
conduction is faster
How is conduction affected over distance?
conduction decreases over distance
What variables effect the distance an electrical signal can travel?
membrane resistance, extracellular resistance, intracellular resistance
What is the length constant (lambda)?
the distance it takes for a change in membrane potential to decay to 37% of its original value
What does it mean if the length constant is large?
the change in membrane potential decreases less over distance (more slowly)
What does it mean if the length constant is small?
the change in membrane potential decreases quickly over distance
How is the length constant calculated?
lambda = square root of rm/(ri + ro)
length constant = square root of membrane resistance divided by the sum of the intracellular resistance and the extracellular resistance
Which of the resistance values used to calculate the length constant is usually so small that it’s not often used in calculations?
the extracellular resistance
What is the equation for the length constant often written as?
lambda = square root of membrane resistance / intracellular resistance
the extracellular resistance is negligible
When will the length constant of the membrane be large?
when membrane resistance is high and intracellular resistance is low
Why does membrane potential decrease over distance?
resistance ie., conduction with decrement
What does conduction with decrement mean?
the change in membrane potential (voltage) decreases over distance because of resistance
What causes increased decay of the change in membrane potential (voltage) along an axon?
high intracellular and extracellular resistance
and low membrane resistance
What causes membrane resistance to be low?
K+ leak channels are always open so there’s always some positive charge flowing out of the membrane
the extent to which this occurs will depend on the number of leak channels
what are the 2 passive membrane properties?
voltage
resistance
What is the calculation involving the 2 passive membrane properties?
Ohm’s Law: V = I*R
What is included in conduction along an axon?
the electrotonic conduction along the axon + the action potential which is produced at specific points on the axon
Is electrotonic conduction faster or slower than the travel of action potentials? explain
faster, action potential generation requires the opening and closing of voltage-gated ion channels
Would a neuron with shorter or longer axons use only electrotonic current flow to transmit signals?
short
electrotonic current flow is only effective for short distances (2-3 mm)
What type of signal transmission is required in neurons with longer axons? why?
action potentials are required because voltage is degraded over time and distance and an action potential ‘boosts’ the signal
What is the ‘cost’ of using action potentials to transmit signals along axons?
while it maintains the voltage of the signal, it’s slower because it relies on the opening and closing of voltage-gated ion channels to activate
What acts as an electrical capacitor?
the membrane
Explain what is meant by a capacitor being an insulator?
the membrane has a thin insulating layer that causes negative charges to build up on one side of the layer because they cannot flow through the insulating layer
this causes the repelling of negative charges and the pulling of positive charges towards the capacitor which creates a current along the membrane
What is the consequence of the membrane capacitor’s function?
current flowing through the membrane resistors is equal to the current flowing into the capacitor
= membrane voltage will change slowly
Explain what happens when you introduce an electrical current into an axon
most of the current initially flows into the capacitor until it is fully charged, then the current will flow into the resistors to change the membrane potential
slow change to membrane potential
Which ligand-gated ion channels will cause depolarization of the membrane?
glutamate receptors (NMDA, AMPA, Kainate)
nicotinic acetylcholine receptors
5-HT3, P2X
Which ligand-gated channels cause hyperpolarization of the membrane? how do they effect the current?
GABAa receptors
glycine receptors
they do this either by shunting a current or hyperpolarizing
What are dendritic spines?
protrusions on dendrites that are the post-synaptic structures of excitatory glutamatergic synapses
T or F: graded potentials can only be generated one at a time
false, they can be generated simultaneously
In what ways can multiple graded potentials be generated at once?
there’s multiple receptor types
some cause depolarizations, some keep the membrane potential hyperpolarized
What is EPSP? What’s the result?
excitatory post-synaptic potential
it causes depolarization
what is IPSP?
inhibitory post-synaptic potential
it causes hyperpolarization
What causes graded potentials to decay over distance and time?
ion leak channels
resistance of cytoplasm
resistance of membrane
T or F: action potentials do not degrade over distance
true
Where is an action potential initiated and by what?
by net graded potential at the axon initial segment
T or F: action potentials require the net graded potential to reach the threshold potential to be initiated
true
What are the 3 phases of an action potential?
membrane:
depolarization
repolarization
hyperpolarization
Describe the steps of an action potential
membrane potential is resting at -70mV
Na+ channels open and Na+ flows into membrane, depolarizing the membrane potential to the threshold potential around -55mV and then a positive mV
K+ channels open more slowly (K+ flows in) and Na+ channels close by inactivation causing repolarization of membrane potential
membrane potential is hyperpolarized as it reaches the equilibrium potential for K+
K+ channels slowly close and membrane potential reestablishes to resting
What is the absolute refractory period?
this occurs when the cell is incapable of initiating a new action potential (ex. during the depolarization phase)
What is the relative refractory period?
the period that’s more difficult to initiate new action potential
usually during repolarization or hyperpolarization
Why was a giant squid used to study axons and action potential?
Huxley and Hodgkin used the giant axon of a squid because it was easier to see
What technique did Huxley and Hodgkin use to study action potentials in giant squid axons?
voltage clamp technique
inject a voltage and clamp it at that value to measure the induced AP
What are 5 major differences between graded potentials and action potentials?
- graded potentials vary in magnitude, whereas AP (in a particular cell) are always the same size and shape
- GP vary in duration, whereas AP are always the same duration (in a given cell type)
- GP degrade with distance, whereas AP do not
- GP occur in dendrites and the cell body, whereas AP are in the axons of neurons (and muscle cells)
- GP are caused by the opening and closing of different kinds of ion channels whereas AP are only caused by the opening and closing of voltage-gated ion channels
What are the cable properties of axons?
each area of an axon has an electrical circuit which contains:
3 resistors: extracellular, membrane, intracellular
a capacitor with 2 conducting materials (ICF and ECF)
Explain how APs are ‘all or none’ - how does this compare to GPs?
they either occur or they don’t (threshold potential must be reached or there’s no AP)
there’s no variation in magnitude/amplitude like there is in GPs
Explain how APs are self-propagating
One AP will trigger another AP in an adjacent area without degradation of the signal
Explain how AP is an electrotonic current
the change to the membrane potential which causes the AP is spread along the membrane
Explain how APs are in a regenerative cycle
entry of ions causes the electrotonic current spread which triggers an AP
How does an axon behave like an electrical circuit?
ions move through the voltage-gated channels = current across the membrane
this current spreads electrotonically along the axon
some of the current leaves the axon and backwards along the external side of the axon (completing circuit)
What are 2 ways to increase conduction velocity of axons?
myelination
larger diameter of axon
if lambda (length constant) is high, how is the speed of conduction effected?
faster speed of conduction with more electrotonic flow
How does membrane resistance affect the length constant and conduction speed?
low membrane resistance = low length constant and decreased conductance speed
How does intracellular resistance affect the length constant and conduction speed?
low ri = increased length constant, increased conduction speed
T or F: the effects of low membrane resistance and low intracellular resistance cancel each other out
false
How is membrane resistance related to diameter of axons?
membrane resistance is inversely proportional to radius = larger diameter, lower membrane resistance = lower length constant and conduction speed
How is intracellular resistance related to diameter of axons?
intracellular resistance is inversely proportional to radius^2 = larger diameter, higher length constant and conduction speed
What are 2 cons of large axons?
they take up a lot of space = limits the number of neurons that can exist in the nervous system
they require a lot of cytoplasm which makes them energetically expensive to produce and maintain
How do neurons compensate for the disadvantages of large axons?
myelination of axons
What are the functions of myelination?
membrane resistance is increased = decreased current loss through leak channels and increased length constant (voltage is maintained for longer distances)
decreased membrane capacitance (insulating layer is thickened to reduce time constant)
overall: increased conduction speed because higher length constant and lower time constant
What along the axon helps boost depolarization?
Nodes of Ranvier
What are Nodes of Ranvier?
the exposed axon bits between the myelin sheaths
where Na+ channels are concentrated
What ion channels are concentrated in the Nodes of Ranvier?
Na+ channels
What are internodes?
the myelinated part of an axon
What is saltatory conduction?
when APs jump from node to node (to areas of high Na+ ion channel concentration)
Is saltatory conduction fast or slow conduction?
very rapid
Where do APs occur along the axon? why?
at the nodes of Ranvier because these are areas with high concentrations of Na+ channels
Where does electrotonic current spread?
through internodes
T or F: there are Na+ channels on myelin
false
What is myelin?
it is produced by
Schwann cells in the PNS and oligodendrocytes in CNS
T or F: oligodendrocytes are the CNS equivalent of the Schwann cells of the PNS
true
Explain how APs are unidirectional
they start at the axon initial segment and only move towards the axon terminal
APs cannot go backwards because the Na+ channels downstream are in the absolute refractory period (cannot be reactivated)
What are the 2 types of synapses?
electrical and chemical
Which of the 2 types of synapses involve neurotransmitters?
chemical synapses
Which of the 2 types of synapses use gap junctions?
electrical
What are gap junctions?
connexins (specialized protein complexes) create aqueous pores between adjacent cells for ions to move (direct communication)
Explain how electrical synapses are forms of direct communication between 2 cells
the electrical signal in the presynaptic cell is transferred to the postsynaptic cell via gap junctions
What are some major differences between electrical and chemical synapses?
electrical:
- bidirectional (ions or currents can move from cell A to B or B to A)
- rapid transmission (electrotonic spread)
- signal received by the postsynaptic cell is always similar to the signal in the presynaptic cell
chemical:
- unidirectional
- slow transmission (docking/fusion of vesicles, diffusion across synapse, signal transduction)
- signal received by postsynaptic cell can be different from the signal in the presynaptic cell
What does it mean for an electrical synapse to be sign conserving?
the signal from the presynaptic cell is the same as the signal received in the postsynaptic cell
T or F: chemical messengers can travel through gap junctions
true
ex. cAMP, ATP, GTP
T or F: opening and closing of gap junctions can be regulated
true, they don’t always have to be open
Are chemical synapses bi- or unidirectional?
unidirectional, only from presynaptic cell to postsynaptic cell
the release of a neurotransmitter across a chemical synapse is controlled by what? explain
calcium
when the presynaptic axon terminal is depolarized, Ca2+ voltage-gated channels open and Ca2+ flows in
influx of Ca2+ causes vesicles to fuse to presynaptic membrane which releases a neurotransmitter
Describe the steps involved in chemical synaptic transmission
action potential reaches presynaptic axon terminal
presynaptic axon terminal is depolarized, Ca2+ voltage-gated channels open and Ca2+ flows in
influx of Ca2+ causes vesicles to fuse to presynaptic membrane which releases a neurotransmitter
neurotransmitter diffuses across synapse and binds to receptor on the postsynaptic membrane
postsynaptic channels open/close
postsynaptic current causes excitatory or inhibitory potential of the cell
neurotransmitter is removed by enzymatic degradation or glial uptake
What evidence is there to suggest that neurotransmitter release in chemical synapses is Ca2+ dependent?
In a study on squid giant synapses:
control: voltage clamp at depolarization of -25mV (from -70mV)
result:
- presynaptic Ca2+ current shows rapid spike then rapid and significant decline before stabilizing
- postsynaptic membrane potential shows slight delay in excitation of membrane potential to approach 0mV
experimental: CdCl Ca2+ channel blocker with voltage clamp at same voltage
result:
- presynaptic Ca2+ current shows no real influx of Ca2+, not much change to current
- no effect on postsynaptic membrane potential
overall: Ca2+ influx is required for release of neurotransmitter which will cause the excitatory response in the postsynaptic membrane potential
Describe Otto Loewi’s study of frog hearts
placed one heart with vagus nerve intact in a chamber of fluid and recorded rhythmic beating until vagus nerve was stimulated
stimulation of vagus nerve slowed heart beat
placed a second heart without direct vagus nerve connection in a second chamber and connected the solution to the first chamber
when the first heart’s vagus nerve was stimulated, the second heart experienced similar effects but at a time delay = there’s an inhibitory effect of the vagus nerve
What did Loewi’s frog heart study suggest about the vagus nerve and heart contractions?
the vagus nerve must be releasing some neurotransmitter (now known to be acetylcholine) that alters heart contractility
How does Ca2+ effect the mechanism of synaptic transmission?
when the presynaptic axon terminal is depolarized, voltage-gated Ca2+ channels are opened, and because [Ca2+] is low inside the cell and and the equilibrium potential of Ca2+ is +130mV, the electrochemical gradients favour the influx of Ca2+ into the cell
increased Ca2+ inside the axon terminal signal to synaptic vesicles containing neurotransmitters
Describe the steps of signal transmission at a chemical synapse
AP reaches presynaptic axon terminal
voltage-gated Ca2+ channels open and Ca2+ flows into cell
Ca2+ binds to synaptotagmin of vesicles containing neurotransmitters
vesicles translocate to membrane and their synaptotagmins bind to SNAREs
vesicles fuse with membrane to release neurotransmitter (exocytosis)
neurotransmitter diffuses across synapse to bind to receptors on postsynaptic cell membrane
binding triggers signal transdusction pathways in postsynaptic cell
What is quantal neurotransmitter release?
vesicles contain many molecules of neurotransmitters (all vesicles within the same neuron contain a similar number of molecules of neurotransmitter)
neurotransmitter molecules are packaged into vesicles which then fuse to the membrane surface and are released by exocytosis
every time a vesicle fuses, the same amount of neurotransmitter molecules are released
if an AP frequency increases, the amount of neurotransmitter released will be step-like because each vesicle is packaged with the same amount of neurotransmitter molecules
neurotransmitters are released into the synapse via exocytosis of the vesicle in the same quantities every time a vesicle fuses to the membrane
What does the quantal release of neurotransmitters mean for the responses in the postsynaptic cell?
the responses will be of discrete sizes because the neurotransmitters are released in discrete packaged amounts
How is quantal response size calculated?
I = npq
where
I = current
n = # of release sites
p = probability of release
q = quantal response size
q = I/np
What determines the probability of neurotransmitter release?
the size of the AP
What proteins and complexes are involved in neurotransmitter secretion?
synaptotagmin
SNAREs (syntaxin SNAP-25 and synaptobrevin)
Describe the steps of neurotransmitter secretion involving the proteins
Loose SNAREs on vesicles and plasma membrane
SNARE complexes form to dock vesicle
Synaptotagmin on vesicle binds to SNARE complex
Ca2+ enters and binds to synaptotagmin to initiate membrane-vesicle fusion / curvature
membranes fuse and exocytosis releases neurotransmitters into the synapse
Where are synaptotagmin and SNAREs located?
synaptotagmin and synaptobrevin are on the vesicle
Syntaxin and SNAP-25 are on the presynaptic cell membrane
How are neurotransmitter receptors classified?
ionotropic or metabotropic
What are ionotropic neurotransmitters? Describe how they work?r
they are ligand-gated ion channels
when a neurotransmitter binds to these receptors, the receptor undergoes a conformational change to open the pore and allow ions to move across the membrane
cause rapid changes to membrane potential
How do ionotropic neurotransmitter receptors affect the membrane potential?
rapidly
What are some examples of ionotropic neurotransmitter receptors?
depolarizing:
glutamate receptor
nicotinic acetylcholine receptors
5-HT3, P2X
hyperpolarizing:
GABAa receptors, glycine receptors
Which of the ionotropic neurotransmitter receptors cause the postsynaptic membrane to depolarize? to hyperpolarize?
depolarize:
- glutamate
- nicotinic acetylcholine
- 5-HT3, P2X
hyperpolarize:
- glycine, GABAa
What are metabotropic neurotransmitter receptors?
a neurotransmitter receptor that undergoes a conformational change with the binding of a neurotransmitter and initiates a signal transduction pathway via a second messenger
causes a signal cascade in the postsynaptic cell
Why are metabotropic receptors slower acting than ionotropic?
ionotropic receptors cause an immediate change to the membrane potential whereas metabotropic receptors initiate a signal transduction pathway
a signaling cascade will eventually send a message to an ion channel to open and that will alter the mmebrane potential
Do ionotropic or metabotropic receptors have longer lasting signals? why?
metabotropic because they affect the transcription and translation of receptors and ion channels
What major class of receptors are metabotropic?
G-protein coupled receptors
ex. metabotropic glutamate receptors (mGluRs)
muscarinic acetylcholine receptors
serotinergic (5-HT1, 5-HT2, etc)
P2Y
GABAb receptors
norepinephrine
dopamine receptors
What 2 ways can postsynaptic potentials be integrated?
spatial summation
temporal summation
Describe spatial summation
postsynpatic potentials originating from different sites change membrane potential
Describe temporal summation
postsynaptic potentials occurring at different times change membrane potential
Do spatial and temporal summation work independently from one another?
no, they work in combination to change the postsynaptic membrane potential
What influences the strength of the response in the postsynaptic cell?
the amount of neurotransmitters released in the synapse and the number of receptors on the postsynaptic membrane
What determines the release of neurotransmitters in the synapse?
the frequency of AP
the probability of release
the number of release sites
How are neurotransmitters removed from the synapse or postsynaptic membrane receptors?
passive diffusion out of synapse
synaptic enzymes degrade them
surrounding cells uptake them
How is the amount of neurotransmitter in the synapse calculated?
rate of release - rate of removal
What are the steps involved in the acetylcholine-cholinergic synapse?
- acetyl CoA is produced in the mitochondria
- choline acetyl transferase converts choline + acetyl CoA = Acetylcholine (ACh)
- ACh is packaged into vesicles by VAChT
- vesicle fuses to presynaptic membrane surface
- ACh is released by exocytosis into the synapse
- ACh binds to receptor on post-synaptic membrane triggering a signal in the postsynaptic cell
- Acetylcholinesterase (AChE) degrades ACh into choline and acetate, terminating signal
Describe the nicotinic acetylcholine receptor
What type of neurotransmitter receptor is nicotinic acetylcholine receptor?
ionotropic
How many ligands are required to bind to the nicotinic acetylcholine receptor to open the channel?
2 ligands
Which ions flux through the channel that the nicotinic acetylcholine receptor opens?
Na+, Ca2+, K+
What is the reversal potential/equilibrium potential for the nicotinic acetylcholine receptor?
close to 0mV
Is the nicotinic acetylcholine receptor excitatory or inhibitory?
excitatory, it depolarizes the membrane
What are the steps involved in the nicotinic acetylcholine receptor binding to neurotransmitters?
2 ligands have to bind for:
closed/resting
activated/open
closed/desensitized
How are the signals transmitted by the nicotinic acetylcholine receptor terminated?
acetylcholinesterase hydrolyzes ACh to shorten response
What type of neurotransmitter receptor are glutamate receptors?
ionotropic
what are the names of the glutamate receptors?
AMPA and kainate
NMDA receptors
What do AMPA and kainate require to open?
glutamate as a ligand
What ions flux when the glutamate receptors, kainate and AMPA, cause the channels to open?
Na+ and K+
What additional feature do NMDA receptors require?
membrane depolarization needs to occur to remove Mg2+ block
require glutamate and either glycine or D-serine to open channel
What ions flux when the NMDA channels open?
Na+, K+, and Ca2+
T or F: NMDA receptors are highly calcium permeable
true
what is the reversal/equilibrium potential of glutamate receptors?
close to 0mV
Are glutamate receptors excitatory or inhibitory?
excitatory, they depolarize the membrane potential
What removes glutamate from the synapse to terminate signalling?
glutamate transporters
How many subunits form a glutamate receptor?
4
what type of neurotransmitter receptor are GABA receptors?
GABAa are ionotropic, GABAb are metabotropic
What ion influxes when GABAa receptors open the ion channels?
Cl-
How do the structure of GABAa receptors compare to that of nicotinic receptors?
they’re similar, both pentameric
What is the reversal/equilibrium potential of GABA receptors?
depends on Cl- which varies from -80- - 60mV
What response do GABAa receptors trigger in the postsynaptic membrane?
hyperpolarizes or shunts current = inhibitory
How is GABA removed from the synapse to terminate the signal?
by GABA transporters
