Lecture 2 Flashcards
What does the movement of a dissolved, charged particle across a lipid membrane depend on?
- charge of particle
- difference in distribution of charged across the membrane (voltage)
- permeability of membrane to the charged particle
What is voltage?
type of potential energy
- how much work it takes to move a charged particle through an electric field
The rate of flow of charges across a membrane is known as current (l) and is defined by?
Ohm’s law
What does I stand for in Ohm’s law?
current
What does V stand for in Ohm’s law?
voltage
What does R stand for in Ohm’s law?
resistance
If there are more channels for a charged particle, what happens to the resistance?
decreases
Overall positive and negative charges are balanced in all physiologic compartments. The electric field __ very rapidly as charges are separated by distance
declines
What is Nernst potential?
membrane potential at which the inward and outward movement of an ion through a channel is balanced and equal
How is a balance reached with reference to Nernst potential?
- diffusional force (movement of an ion down its concentration gradient)
- electrical force (attraction or repulsion based on the charge of an ion and the charge across the membrane)
The __ potential describes movement of an ion very close to the cell membrane, across channels in that membrane
Nernst
What describes the energy gradient?
Nernst potential
At rest, neurons typically have a membrane potential that is close to the Nernst potential for __
K+
The intracellular concentration of K+ relative to the extracellular concentration is?
-75 mV
At rest, the only ion channels that are open are K+ channels – these channels are known as “__” channels because they are always open
leak
What does the membrane potential of any cell depend on?
The relative permeability of the membrane to each ion
The concentration of the ion on either side of the membrane
If the membrane potential is close to the Nernst potential of a particular ion, it usually means ?
that the membrane is more permeable to that ion
What is the concept of the Goldman Field equation?
When the membrane is permeable to more than one ion, then the __ __ equation is necessary to predict the membrane potential
Goldman Field
T/F: Most channels are selective to relatively few ions – those ions typically have the same charge
True
T/F: Membranes are poorly permeable to uncharged particles
false, charged
Does membrane permeability and membrane potential have quick or slow? Why?
Quick because they are dynamic and can respond to a variety of stimuli
Channels will change their open/closed states depending on what they’re “built” to detect, what are examples?
Voltage – voltage-gated channels
Stretch or mechanical deformation – mechanoreceptors or osmoreceptors
Intracellular messengers
Extracellular messengers – ionotropic receptors
Where do action potentials happen?
axon, axon hillock, and synpatic terminal
What are the attributes of an action potential?
Requires the presence of sodium voltage-gated channels (or sometimes calcium voltage-gated channels)
Relies on positive feedback
Always results in a membrane voltage change that is the same size
Occurs very quickly – the membrane becomes more positive (depolarized) in a matter of milliseconds
When a neuron is __, it is more likely to fire an action potential
depolarized
What channels help to quickly terminate the action potential?
K+ VGC
What do the axon hillock, axon, and synaptic terminal all posses a large population of?
sodium voltage-gated channels (Nq+ VGC)
What happens during step 1 of an action potential?
The Resting Membrane Potential:
The Na+/K+ ATPase uses ATP to pump Na+ out of the axon, and K+ in
- K+ concentrations are high inside the axon, and low outside (vice-versa for Na+)
- K+ is high inside the axon, so it diffuses out - diffusional, or chemical, force acting on K+
- Membrane becomes negative inside the axon - Negatively-charged proteins, ions cannot leave the cell with K+
The attractive force of the negatively-charged membrane balances out the diffusional force driving K+ out
- This balance establishes the resting membrane potential at about -70 mV (inside membrane negative)
What happens during step 2 of an action potential?
The inside of the axonal membrane becomes more positive, and a Na+ VGC opens
- channels are opened by more positive charges inside membrane (positive feedback)
- threshold = membrane potential at which all Na+ VGC will end up opening (~ -55 mV)
Na+ VGC opening leads to other Na+ VGC opening, eventually all open
- positive feedback, Na+ diffuses into the cell, making membrane more positive, allowing more Na+ in
Inside of the axon becomes completely depolarized
- diffusion gradient (high Na+ outside, low inside) as well as electrical force (inside negative) drives Na+ into the cell
K+ VGC open, Na+ VGC close after ~ 1 msec
How are channels opened in an action potential?
by more positive charges inside membrane (positive feedback)
What happens during step 3 of an action potential?
Na+ VGC are closed, no further Na+ entering the axon
- close after about 1 msec
- Are unable to open for 1-2 msec – they are “locked”
- After 1-2 msec, Na+ VGC will “unlock” – but only if the membrane is replolarized (becomes inside-negative again)
K+ rapidly leaves the axon
- high K+ inside axon and positive charge inside the membrane strongly drive K+ out
- K+ VGC and regular K+ channels are both open, allowing rapid K+ exit
Na+ VGC are ready to re-open:
- when membrane potential is -70 mV (repolarization)
- after they’re “unlocked” (1 – 2 msec after closing)
What are the two gates of the sodium voltage-gated channels?
activation gate
inactivation gate
When does the activation gate open of the sodium voltage-gated channel?
as soon as threshold is reached (i.e., membrane depolarizes to -55 mV
What does the inactivation close of the sodium voltage-gated channel?
very soon after the activation gate opens, after Na+ has rushed into the cell
The inactivation gate of the sodium voltage-gated channel will not open again unless?
1-2 msec has passed since it has closed (it’s “locked”)
The cell membrane becomes inside-negative again (repolarized)
The potassium voltage-gated channel does not have an inactivation gate, when does it ope and close?
it opens when the cell depolarizes, and closes once the cell is inside-negative again
T/F: Potassium voltage-gated channel is faster to open than the sodium voltage-gated channel
False, slower
What happens during the absolute refractory period?
Inactivation gate of the Na+ VGC is closed
Another action potential is impossible until this gate opens
What happens during the relative refractory period?
Inactivation gate is open, activation gate is closed for the Na+ VGC
The cell is hyperpolarized – the membrane potential is lower than resting membrane potential
A larger stimulus is necessary to reach threshold
What are properties of action potentials?
All-or-none events
Initiated by depolarization
Have constant amplitude
Have constant conduction velocity along a fiber
What is meant by an action potential being an all or nothing event?
- Begin when a threshold voltage (usually 15 mV positive to resting potential) is reached
- There are no “small” or “large” APs – each one involves maximal depolarization –> all Na+ channels open once threshold is reached
What is meant by an action potential having a constant amplitude?
- Action potentials don’t summate – information is coded by frequency, not amplitude
- The size of the depolarization stays the same size no matter how far it travels along axon
What is meant by an action potential having constant conduction velocity along a fiber?
Fibers with a large diameter conduct faster than small fibers.
- Myelinated fiber velocity in m/s = diameter (um) x 4.5
- Unmyelinated fiber velocity in m/s = square root of diameter (um)
If the diameter of myelinated axons increasing, what happens to the velocity?
increases
Are myelinated or unmyelinated axons faster?
myelinated
What is continuous conduction?
The action potential is reproduced all the way along the length of the axon – continuously
Where does saltatory conduction occur?
node of Ranvier
Where are the only parts of the axon expressing voltage-gated channels?
nodes of Ranvier
What does myelin insulation allow?
electrical field from the depolarization to “jump” to the next node of Ranvier
Therefore it’s the positive “__ __” from one node of Ranvier that brings the next node of Ranvier up to threshold
electric field
What are chemical synapses associated with?
excitable cells
What is the “chemical” part of the chemical synapse?
The presynaptic neuron releases a neurotransmitter (NT) that binds to receptors embedded in the post-synaptic cell membrane
The presynaptic terminal of the axon is the site of?
neurotransmitter release
What happens after the presynaptic neuron releases a neurotransmitter (NT) that binds to receptors embedded in the post-synaptic cell membrane?
the neurotransmitter cross the synaptic cleft
T/F: Binding of the neurotransmitter to a receptor can affect the postsynaptic cell in a wide variety of ways
True
Where is the synapse usually?
between a dendritic spine or an axon terminal – the dendritic spine expresses the receptor for the NT
Where are vesicles synthesized and packaged by? What transports them down the axon?
rER & Golgi, microtubules
What is fast axonal transport?
the “molecular motor” kinesin transports the vesicles towards the synaptic terminal, like a train along a track of microtubules
Where are neurotransmitters (non-peptide) synthesized?
in cytosol of presynaptic terminal & transported into vesicles
How are neurotransmitters transported into the vesicle?
using proton gradient generated by a proton pump
Vesicles bind to the __ within the presynaptic terminal cytoskeleton and are transported to release sites (active zone) close to the __
actin; synpase
What are the 6 basic steps of NT release?
- AP arrives at the presynaptic terminal
- Depolarization leads to opening of voltage-gated calcium channels
- Calcium enters the presynaptic terminal (as per its Nernst potential)
- Calcium binds to a protein associated with neurotransmitter-filled vesicles
- Neurotransmitter is released into the cleft as the vesicles fuse with the presynaptic membrane
- Neurotransmitter binds to a receptor
How is calcium entry mediated in neurotransmitter release?
Ca+2 VGC
The whole point of the action potential is to open __ VGC in the presynaptic terminal
Ca+2
What is accomplished once the action potential has ?
Ca+2-induced exocytosis of NT into the synaptic cleft
T/F: Vesicle released needs to be highly regulated, but not quick
True
What are key players in vesicle release?
v-SNAREs
t-SNAREs
complexin
synaptotagmin
What are v-SNAREs?
a protein complex of proteins attached to vesicles
- They “force” the vesicle to fuse with the presynaptic membrane and dock with t-SNARES
What is an example of v-SNARE?
synaptobrevin
What is a t-SNARE?
a protein complex attached to the pre-synaptic membrane –> “grabs” the v-SNAREs
What are examples of t-SNAREs?
Syntaxin and SNAP-25
What is complexin?
a molecule that prevents premature release after v-SNAREs and t-SNARES engage with each other
What is synaptotagmin?
a calcium-binding protein
- When calcium binds, it “knocks” complexin off the v-SNARE-t-SNARE complex
What are the steps of vesicle release?
- v-SNARES and t-SNARES “zipper” together
- Synaptotagmin and complexin prevent premature fusion and release after zippering - AP –> depolarization –> Ca+2 VGC opening –> calcium influx into the pre-synaptic terminal
- Calcium binds to synaptotagmin –> disengagement of complexin
- The synaptic vesicle fuses when complexin disengages –> release of NT into the synapse
- The v-SNAREs and t-SNARES disengage, and the vesicle is re-used
- This occurs after intracellular calcium levels decrease
What impairs the assembly and function of v-SNAREs and t-SNAREs –> impairing fusion of vesicles w/ the presynaptic membrane?
toxins produced by Clostridium botulinum (botox)
How is botox used therapeutically to reduce muscle spasticity, treat migraines and decrease wrinkles?
Prevents release of acetylcholine from motor neuron pre-synaptic terminals, which is necessary to excite contraction in skeletal muscle
What does Botox A bing to?
SNAP-25 (v-SNARE)
What are 4 ways neurotransmitters removed?
- Degraded by enzymes in the synapse
- Reabsorbed by nearby astrocytes
- Reabsorbed by the pre-synaptic terminal
- Diffuse out of the cleft and carried away by blood
The effects of NT can vary, what are some examples?
Different neurons will release different NTs from the presynaptic terminal
Different postsynaptic cells may contain different receptors
Some NTs cause cation channels to open
Many NTs cause a G-protein or other intracellular cascade of second messengers
What does a neurotransmitter causing a cation to open result in?
- Depolarization for sodium and (to a lesser extent) calcium
- Hyperpolarization for potassium
What can NTs that cause a G-protein or other intracellular cascade of second messengers, result in?
open or close channels for longer periods, change kinase activity, change gene expression
What do ionotropic receptors do?
open an ion channel when they bind to their ligand
What are examples of ionotropic receptors?
NMDA receptor
Nicotinic acetylcholine receptor
GABA(a) and glycine receptors
What is the function of the NMDA receptor?
binds the NT glutamate –> sodium and calcium channel opening
What is the function of the Nicotinic acetylcholine receptor?
binds to acetylcholine –> sodium channel opens
What is the function of GABA(a) and glycine receptors?
bind to GABA and glycine respectively –> Cl- channel opens
Many (most?) metabotropic receptors are linked to _-__ signaling
G-protein
What receptors does Ach - excite neurotransmitter bind to?
nicotinic
M1, M3, M5
What signal does Acetylcholine (excite) neurotransmitter have once it binds to nicotinic and M1, M3, M5 receptors?
- ionotropic, sodium channel
- increase in calcium (metabotropic)
What receptors does Acetylcholine (inhibit) neurotransmitter bind to?
M2, M4
What signal does acetycholine binds to M2, M4 metabotropic receptors, what happens?
decrease in calcium or cAMP or opens a G-protein-gated K+ channel
What happens when GABA binds to GABAa?
inhibits
inotropic, chloride channel
What happens when Glutamate excites NMDA & AMPA?
ionotropic, sodium + calcium channels
What happens when Glycine inhibits strychnine-sensitive receptors?
inotropic, chloride channel
What happens when norepeinphrine excites alpha-1 and beta-1 receptors?
increased IP3 and calcium (metabotropic)
increased cAMP (metabotropic)
What is acetylcholine responsible for?
Nicotinic – the NT of the neuromuscular junction, also widely expressed throughout the brain
Excitatory muscarinic – important for cognitive function, memory
Excitatory and inhibitory muscarinic are key for the activity of the autonomic nervous system
What is the most important inhibitory NT of the “intracranial” CNS
GABA
What is most important inhibitory NT of the spinal cord?
Glycine
What is the most common excitatory NT of the CNS?
glutamate
__ receptors are very important for learning and memory.
NMDA
What are the functions and roles of norepinephrine?
excitatory autonomic nervous system functions, also cortical and limbic system roles
What happens if a neurotransmitter binds to an inhibitory receptor?
results in dendrite hyperpolarization (membrane becomes more negative)
What happens if a neurotransmitter binds to an excitatory ionotropic receptors?
dendrite depolarization (membrane becomes more positive)
Activation of ionotropic receptors bring about graded potentials in the dendrites and cell body
If the depolarization or hyperpolarization is large enough, this may be change the membrane potential at the __ __
axon hillock
Where are ionotropic receptors located?
dendrites or cell body
What is graded potential?
any change in membrane potential that doesn’t result in an action potential
What type of potential includes changes in membrane potential that are below the threshold for an action potential or occur in areas of the cell that do not have Na+ VGCs?
graded potentials
What are properties of graded potentials?
They get smaller (decremental) over time and the further they travel along the cell membrane
They can vary in magnitude
They can “add together”, or summate
They can be excitatory (depolarization) or inhibitory (hyperpolarization)
Even if an EPSP is higher than threshold, no AP will occur unless?
Na+ VGC are present
If neuron gets a lot of EPSP at the same time may cause?
depolarization
Once that graded potential reaches threshold, what happens?
will generate an action potential
If multiple EPSPs from different sites meet at the same time, same place on the membrane, what is this called?
spatial summation
If multiple graded potentials add up in a “staircase” fashion over time, what is this called?
temporal summation
T/F: Many different axons synapsing on one neuron can result in a wide array of EPSPs and IPSPs
True
Where is the net result of all EPSPs and IPSPs integrated?
axon hillock
What happens if the graded potentials bring the hillock to threshold?
an action potential (or strings of action potentials, if the graded potential lasts many milliseconds)
Metabotropic receptors can have very long-lasting effects that include?
protein synthesis and intracellular signals
What fibers are the fastest?
A fibers
Which fibers are non-myelinated?
B Fibers, C Fibers
What are A fibers used for?
- Large sensory nerves for touch, pressure, position, heat, cold
- Final common pathway for motor system
- Largest ones are directed to proprioception*
What is the role of B fibers?
From viscera to brain and spinal cord, autonomic efferents to autonomic ganglia
What is the role of C fibers?
- Impulses for pain, touch, pressure, heat, cold from skin and pain impulses from viscera
- Visceral efferents to heart, smooth muscle and glands
What is the origin or graded potentials?
mainly in dendrites and cell body
What is the origin of action potentials?
arise at trigger zones & propagate along the axon
What types of channels are involved in graded potentials?
ligand-gated or mechanically gated ion channels
What types of channels are involved in action potentials?
voltage-gated channels for Na+ and K+
What conduction is involved in graded potentials?
Decremental; permit communication over short distances, degrade over long distances
What conduction is involved in action potentials?
Propagate and thus permit communication over longer distances
If the refractory period is not present, what can occur?
summation
