PSL201 Week 3

______ potentials are small and communicate over short distances; ______ potentials are large and communicate over long distances

Graded; action

What happens during depolarization?

Opening of Na channels causes membrane to move towards +60mV, which is Na's eq potential
However, it only reaches about +30mV because a ms after Na channels open, they start to inactive so MP never reaches +60

What is the most common local anesthetic that dentists use to "freeze you"? How does it work?

Lidocaine/voltage gated Na+ channel blocker stops Na from entering nerves at site of the pain, so no AP can be generated

What happens during repolarization?

Voltage gated K channels open when membrane is depolarized, allowing K+ to leave
Since depolarized, K+ even more driven to leave cell (electric force)

What happens during hyperpolarization? Why does it happen?

Voltage gated K+ channels close slowly
Membrane overshoots/hyperpolarizes

Describe the membrane’s permeability for Na and K during different phases of an AP

PNa+: sharp rise of permeability during depolarization, which is short-lived
PK+: rises gradually and slowly, reaches a peak during final phases of the AP, remain open for longer even after brought back to resting state (hyperpolarization)

What kind of potentials bring the membrane to threshold?

Graded potentials

During an AP, why does the membrane potential not reach ENa (sodium’s equilibrium potential)?

Because Na+ channels close and K+ channels open

After an AP, what restores the resting membrane potential?

The Na/K pump

Describe the activation gate of the voltage-gated Na+ channel, and when it is open and closed

Voltage dependent and postive feedback
Opens at threshold and depolarization
Closed at resting state

Describe the inactivation gate of the voltage-gated Na+ channel, and when it is open and closed

Voltage and time dependent
Open at resting state and during depolarization
Closes during repolarization

What happens when the voltage-gated Na+ channel inactivation gate is closed?

Blocks any further sodium influx/diffusion across the membrane

Describe voltage-gated K channels

One gate, depends on voltage and time, negative feedback (operate to bring membrane back to resting potential after depolarization)

What happens to Na channels when stimulus reaches subthreshold?

Opens some Na channels but not enough to overcome the efflux K

Describe the all or none principle

APs from threshold and supra-threshold stimuli are the same magnitude

Describe what the Na channels are like during absolute vs relative refractory period

Absolute: none of the voltage gated Na channels are reactivated
Relative: some of the voltage gated Na channels are reactivated

Describe how you can completely block the membrane from generating an AP using KCl

Keep membrane depolarized permanently, so voltage gated Na+ channels are inactivated. Do this by destroying the concentration gradient for K, using a KCl injection (this is used to kill people). KCl introduces more K in the extracellular space, K no longer driven to leave the cell. This will result in K not leaving the cell, meaning it will be less negative (more positive), resulting in permanent voltage gated Na channel inactivation, membrane will remain in the absolute refractory state, no longer excitable. Heart can no longer beat!

What are the 3 consequences of refractory periods?

All or non principle, frequency coding, and unidirectional propagation of APs

Describe frequency coding

The intensity of the stimulus is encoded by the frequency of the AP; stronger stimulus will result with higher frequency AP firing
Stronger/longer lasting graded potential may generate many APs in close succession

Describe how refractory period allows spread of AP to be unidirectional

The patch of the membrane that was recently depolarized is undergoing absolute refractory period, cannot generate another AP

Describe 3 factors that affect propagation

Refractory period (unidirectional), axon diameter, and myelination

Will propagation be faster on an axon larger or smaller in diameter, and why?

Faster for larger axons, since less resistance, faster

On a myelinated axon, where are voltage-gated Na+ channels clustered?

Nodes of Ranvier

Describe saltatory conduction

In myelinated axons
AP jumps from one node to the next
Current moves rapidly and passively underneath the myelin sheath

What prevents dissipation of Na+ and K+ concentration gradients?

Na+/K+ pump

Describe electrical synapses

- Two neurons (or a neuron and glial cell) linked by gap junction
- Gap junctions are bridged by connexins which allow small ions and depolarization to cross
- Rapid
- Usually bidirectional communication
- NTs not required

What are some examples of places we see electrical synapses?

Retina, cortex, brainstem (breathing), and hypothalamus (neuroendocrine neurons)

Describe chemical synapses

- Synaptic cleft
- Unidirectional
- NTs, receptors, enzymes, reuptake molecules
- Usually synapse on dendrites (axodendritic)
- Some synapse on soma (axosomatic) or axons (axoaxonic)

Define axodendritic, axosomatic, and axoaxonic

Axodendritic: axon synapse on dendrites
Axosomatic: axon synapse on soma
Axoaxonic: axon synapse on axon

True or false: In chemical synapses, vesicle release is probabilistic

True

Why do Ca2+ channels open at the axon terminal?

Depolarizing current of AP opens voltage gated Ca channels

What are the 3 ways to remove NTs from the synaptic cleft?

Break down NTs with an enzyme
Transport NTs out of the synaptic cleft into the pre or post synaptic cells or into the astrocytes
NTs diffuse out of cell

Describe how nerve gases work to kill someone

They block the removal of NTs from the synaptic cleft by inhibiting Acetylcholinesterase
This continues to cause depolarization, lots of involutory reactions (e.g. salivation, defecate, etc.), makes people vey tired, no longer able to breathe
These chemicals occur naturally as venoms and poisons, sometimes used to treat diseases

What is one of the most commonly prescribed antidepressants, and how do they work?

- SSRI (selective serotonin uptake inhibitor)
- Serotonin levels are lower in depressed individuals
- SSRIs lead to more serotonin available at the synapses
- Example: Prozac

Describe synaptic delay and what causes it

- 0.5–5 msec between arrival of an action potential and change in postsynaptic Vm
- Caused by changes in [Ca2+] entry, vesicle docking, and release of neurotransmitter
- Not related to diffusion of neurotransmitter across the synaptic cleft

What are the two classes of receptors at the synaptic cleft?

- Channel-linked receptors/ionotropic receptors
- G protein–coupled/metabotropic receptors

Describe channel-linked receptors/ionotropic receptors and how they work

- Ligand-gated channels
- Fast-acting (fast change in Vm)
- Channel closes as soon as NT leaves

Describe G protein–coupled/metabotropic receptors and how they work

- Slow acting
- NT binds to the receptor, which activates G protein
- Activation of G protein results in opening or closing of an ion channel some distance away (direct coupling)
- Slow-acting (slow change in Vm)

Describe G protein–coupled/metabotropic receptors coupled with second messenger systems

- Activated G protein activates or inhibits enzymes, which results in increase or reduction of second messengers
- Second messengers can be cyclic AMP or GMP or others
- This results in either opening or closing of ion channels
- Can also lead to internal changes that produces other cell responses

Postsynaptic Potential (PSP)

Change in membrane potential in response to receptor-neurotransmitter binding

Describe an advantage of slow EPSPs

Amplification effect: due to second messenger systems
where one NT bound can create many second messengers. This gives us an advantage, such as detect a minute
amount of perfume in the air (metabotropic takes time). Change is slow because it has to go through enzyme activates first

_____ tend to be very specific and precise; ____ tend to be very general and not accurate

IPSPs; EPSPs

What channels might open for inhibitory synapses?

K+ or Cl-

What happens if K+ channels open for inhibitory synapses?

K+ channels open, K+ moves out down its concentration gradient
IPSPs generated (hyperpolarization)

What happens if Cl- channels open for inhibitory synapses?

Two possibilities:
1. Cl– moves in, resulting in IPSPs (hyperpolarization):
- Post-synaptic neuron is actively pumping Cl out of the cell by using the Cl pump
- Binding of NT opens Cl channel, and Cl wants to come in, since there are more Cl outside due to the Cl- being pumped out
- This hyperpolarizes the membrane

2. Cl– stabilizes membrane potential
- The post-synaptic membrane is lacking the active Cl transporters (the Cl pumps), it just has Cl leak channels (free diffusion)
- Binding of NT to receptors opens Cl channels, causes nothing to happen to membrane since it is already at equilibrium
- No change in membrane potential, it remains at resting level
- This prevents excitation, leading to inhibitory effect

Divergence

A single presynaptic neuron connects with many post-synaptic neurons

Convergence

Many pre-synaptic terminals converge onto a single post synaptic neuron

Summation

Adding effects of graded potentials

Temporal summation

One synapse through time

Spatial summation

Several synapses at the same time

Frequency coding

The degree of depolarization at the axon hillock is signaled by the frequency of action potentials
Summation affects depolarization, therefore it influences frequency of action potentials

Presynaptic modulation definition + 2 types

Definition: the regulation of communication (NTs) across a synapse. The modulating neuron's axon terminal connects to the axon terminal of the pre-synaptic neuron. The modulating neuron does not generate a PSP, but it modulates the NTs that will be released from the presynaptic neuron
Types: presynaptic facilitation (release of NTs is enhanced) and presynaptic inhibition (release of NTs is decreased)

Describe the purpose axoaxonic synapses

Axoaxonic synapses function as modulatory synapses (engage in presynaptic modulation)

Describe presynaptic inhibition

Modulating neuron releases NTs that causes the presynaptic neuron to release less NTs

Describe the differences between axoaxonic synapses vs axodendritic and axosomatic synapses

Axoaxonic: excites or inhibits one synapse (increase or decrease of NT release), selective
Axodendritic and axosomatic: excite or inhibit postsynaptic neuron, nonselective

What is the most abundant neurotransmitter in PNS?

Acetylcholine

What is the only NT used in the somatic NS?

Acetylcholine

Describe the synthesis of acetylcholine

- Acetyl CoA + choline —> acetylcholine + CoA
- Synthesized in axon terminal
- Choline acetyl transferase (CAT) = enzyme for synthesis

Describe the breakdown of acetylcholine

- Acetylcholine —> acetate + choline
- Occurs in synaptic cleft
- Acetylcholinesterase (AChE) = enzyme of degradation

Describe the effects of Curare, an Ach competitive antagonist

If you block Ach from doing its job, then voluntary movements stop
As fixation occurs, respiratory system muscles unable to contract

What are the two types of cholinergic receptors?

Nicotinic (ionotropic) and muscarinic (metabotropic)

The effect of a NT is determined by the _____ and NOT the _____

receptors; ligand

Describe how nicotinic cholinergic receptors work

- When Ach binds at the binding site, conformational change happens to open the pore in the receptor to allow Na and K to cross the membrane (Na in, K out)
- More Na into cell than K leaving, so we end up with EPSPs
- Also respond to nicotine --> effect of smoking cigarettes is mediated by these receptors
- Smokers may be somewhat protected from Alzheimer's

Describe how muscarinic cholinergic receptors work

- Binding of Ach activates G protein, which will either open or close ion channels, depending on which type of muscular cholinergic receptor it is
- G-protein activation may activate other enzymes to catalyze production of second messengers
- Second messengers can have variety effects on the post-synaptic membrane, such as open or close channels, effects could be EPSPs or IPSPs
- Heart: parasympathetic nerve that innervates the heart releases Ach, which binds to M2 muscarinic receptors, which slows down HR

What are biogenic amines?

Class of NTs that have an amine group

Catecholamines (what are they derived from, and 3 types)

- Derived from tyrosine
- Dopamine, Norepinephrine (noradrenalin), Epinephrine (adrenalin)

Serotonin (what it is, what it is derived from?)

- A type of biogenic amine
- Derived from tryptophan
- Main location: brainstem
- Functions: regulating sleep & emotions
- Synthesis of serotonin is directly related to plasma concentration of tryptophan
- Levels also increased by carb-rich meals: increased insulin levels --> elevated plasma and tryptophan levels
- Since SSRIs elevate serotonin levels in the synaptic cleft, it wont work if having a diet low in tryptophan! (need it to synthesize serotonin in the first place)

Histamine (what it is, what it is derived from?)

- A type of biogenic amine
- Derived from histidine
- Main location: hypothalamus
- More commonly known for paracrine actions
- Released in response to allergic reactions
- In CNS, it is associated with wakefulness, effects the histaminergic system which helps keep you awake
- Explains why some allergy medications make you drowsy, as main ingredient is antihistamine

What are some amino acid NTs?

- Inhibitory: aspartate, glutamate
- Excitatory: glycine, GABA
Not very abundant in CNS

Neuropeptides examples

Endogenous opioids (enkephalins & endorphins), Oxytocin, Substance P

Describe gas neurotransmitters, such as nitric oxide

- Not stored, make them on the spot as needed (since it’s a gas)
- Release determined by rate of synthesis by nitric oxide synthetase
- Diffuses to target
- Effects only last about a second