Week 1: The Membrane

The cell membrane

• what is it composed of

• what can go through the membrane without help

• What cannot go through (impermeable)

• the cell membrane is composed of phospholipids

• lipid-soluble molecules and gases can go through the membrane without help

• Impermeable to organic anions (proteins)

Membrane permeability

• What factors affect permeability: 3 factors

• Definitions of permeable

• What is not permeable and what 2 things can help them cross

• The size, lipid solubility and charge of the molecule

  • Bigger size cannot get through

  • Charges cannot get through

  • More lipid-soluble molecules can get through

• Permeable: something that can be able to go through the membrane by ANY MEANS (either diffusing or without help)

  • Gasses are diffusable

• Polar molecules and ions need protein channels or carriers to cross

Types of diffusion

• name them only

• 2 types

• Simple diffusion

• Facilitated Diffusion

Simple diffusion

• what molecules can do this

• How does simple diffusion work

  • What direction does it move?

  • What is proportional to its rate of diffusion?

  • What is not required for this diffusion

• Is the process continuous or discontinuous?

• lipid soluble and small molecules and gasses can do this

• Through pores or pass directly through the lipid bilayer

• Process

  • Goes directly through the lipid bilayer or through pores

  • Goes down the concentration gradient

  • The greater the gradient the faster the rate of diffusion (proportional)

• No ATP/energy required

Facilitated Diffusion

• How is it similar to the simple diffusion (2 factors)

• What makes it different from simple diffusion (2 factors)

• Explain the process of facilitated diffusion (3 steps)

• Explain what transport system saturating is and why does it happen?

• Is the process continuous or discontinuous?

• Similar to the simple diffusion

  • No energy is required from ATP

  • Goes down the concentration gradient

• Different from simple diffusion

  • Transports specific molecules

  • Involves an assistance of a carrier protein

• Step of facilitated diffusion

  • Molecule binds to the carrier protein

  • Carrier protein undergoes a conformational change

  • The change allows the translocation of the molecule to the other side

• Transport system can be saturating

  • This when there is too must molecule that needs to be transported than there are carrier proteins

  • Molecules must wait until the transporters can do their job

• Process is discontinuous

Primary Active transport

• What does the molecules move

• What does it require that makes it different from diffusion

• how is it similar to facilitated diffusion (2 factors)

• Give a common example of a facilitated diffusion

• Molecules move against the gradient

• Requires ATP hydrolysis/catabolism to produce energy

• Similar to facilitated diffusion

  • Will move specific molecules: selective

  • Molecules binding to the carrier protein will result in a conformational change

• ATPases (na+/K+ pump)

Secondary Active Transport

• How does the molecule move through the gradient

• What doesn’t need compared to primary active transport

  • Instead what else does it use instead to power the transportation (what does it depend on and what happens to the protein)

• Against the gradient

• Does not need ATP hydrolysis

• Process

  • Secondary = 2 solutes

  • Dependent on the primary active transport: One down the gradient simultaneously power the movement of another solute up the gradient

  • Proteins undergoes conformational change during binding of substance/ions

Gated channels

• What forms the channel and what is this also called

• What is a pore loop what does it do

• What is a gate?

• What are the 2 types of gates

  • Explain what is required for each gate to open

  • how does it open (explain what happens to the protein)

• 4-5 subunits of membrane spanning proteins forms pores

• A pore loop is inside the membrane

  • Function: creates a selectivity filter

• Gate: a protein that functions to either close or open the channel under certain conditions by changing between two shapes

• Types

  • Ligand Gated

    • the binding of a chemical agent to a receptor (part of the chemical signalling ) to trigger events like an activation of an enzyme or a ion channel to open

    • very important for synaptic transmission

  • Voltage gated

    • Voltage gradient causes channels to undergo conformational change to create an open pore

    • Use of the s4 segment of the protein

      • Positively charged attracted to the negatively charged inner membrane surface to close the pore (-70 mV)

      • However depolarization (-50 mV inside) is not enough attract and the wings move towards the outer membrane and allows the pore to open

Endocytosis

• In one sentence describe endocytosis

  • What mediates this process and why?

• the inwards pinching of the membrane to form a vesicle

  • Receptor mediated to allow the capture of specific proteins to the inside of the cell

Exocytosis

• main definition

• Types of exocytosis

  • What occurs at each type

  • What is the purpose of each type (when does this occur)

  • What is the require for the more greater exocytosis type

• def: The partial/complete fusion of vesicles to the membrane for bulk trans-membrane transport of specific molecules

  • Inside to outside

• Intracellular materials to the secreted or delivered to the membrane

• Exocytosis 1: Kiss and Run - fast mechanism

  • Dock and fuse at specific locations called fusion pores

  • Connecting and disconnecting multiple times before fully emptied (each kiss only releases a bit of contents)

  • Low rate of signaling - slow because doing it multiple times

• Exocytosis 2: Full Exocytosis

  • The complete fusion to the membrane

  • Releasing all contents at once

  • Purpose: for delivery of membrane proteins and higher levels of signalling

  • Membrane will become too big and contents inside don’t change so must be counterbalanced by endocytosis to stabilize the surface area

What do all cells generate?

What do all cells have?

membrane potential

have na+/K+ pumps

What two conditions are required for membrane potential

1. Create concentration gradient: enzyme ion pumps actively transports selected ions across membrane to form the gradient

2. Sem-permeable membrane: membrane must be able to diffuse a certain ions than others

• After these 2 conditions the movement down the concentrations gradient will create an electrical gradient

• Why is Na+/K+ pumps important?

• What does the pumps require in order to function (recall active transport)

• How much and movement of Na+ and K+ for each time

• How much energy out of the entire body is needed

• Overall voltage with just pumps

• All cells have Na+/K+ pumps to generate MP

  • The Na+/K+ depends on ATPase enzyme to functions: (Na+ moves out of the cell, K+ into the cell through the breaking of ATP)

  • One ATP broken = 3 NA out and 2 K in

  • ⅓ of energy of the body needs in this process

  • Overall -10 mV inside due to only this pump (more + ions out which makes sense)

K+ channels

• purpose of K+ channels (recall the voltage of the Na+/K+ pumps vs usually voltage gradient in resting potential)

• How does K+ work?

  • How does the diffusion work

  • How does the diffusion stop

• Due to the increase of K+ ions inside the cell, K+ channels help in the diffusion of K+ ions out of the cell and down concentration gradient

• This will stop when the diffusion of K+ is prevented by the electromagnetic force of the membrane (very high positively charged surface area of the membrane prevent K+ from entering)

With both na+/K+ pumps and K+ channels, what is the resting membrane potential of the cell

• give number of the voltage

• Also explain what causes this number to occur (explain the movement of ions)

-70 mV

• the movement of na+ and K+ ions to move out

Equilibrium Potential

• what happens when the equilibrium potential is reached

• What factors determines equilibrium potential

• The cation diffusion to the outside is balanced by the cation being pushed inwards due to the overall negative charge inside the cell

• Mainly determined by the concentration gradient

The Nernst Equation

• What does this equation describe

• What doe the results indicate

• One condition it must follow for the equation results to be accurate

• Example of K+ equilibrium potential

  • What is the results number and is it accurate, if not why?

• Describes the diffusion and the electrochemical repulsion force

• The results describes the inside potential difference compared to the outside

• Result will only make sense if there is only one ion involved

• E.g. K+ Equilibrium Potential

  • EK+ = (RT/F) ln([K+]o /[K+]i) = -90 mV (equilibrium potential for K+)

    • However, usually the cell is -70 to -80 mV

• From the Ernest equation previous lecture, for K+ ions the resting membrane is calculated as -90 mV (however it is not)

  • Reason

    • Rest: K+ is most permeable, Na+ and Cl- somewhat diffusing (low permeability) at the same time

  • Solution: expand the Ernest equation to the Goldman Equation

Goldman Equation Sample

• P represents the permeability coefficient

• T is temp

• R is gas constant

• F is the Faraway constant

• []o: concentration out

• []i: concentration in

Na+ Equilibrium Potential

• what is the movement of Na+

• When it reaches equilibrium what happens to the movement (explain why it stops)

• Provide equilibrium potential for na+

• If the membrane properties change to make the membrane most permeability to Na+, the Na+ will go in (influx), with an net cation accumulation inside to make the membrane potential positive

  • ENa+ = +60 mV

Cl- Ions

• Movement of the cl- ions and why? (what is mainly inside/out of the cell that causes this movement)

• Large proteins are located on the inside, the ions are only moving outside to the EC space

• Overall negative concentration outside

• Not due to active pump; due to anion proteins

Na+ Channels

• what is the important of Na+ channels?

• What type of gated channel is Na+?

  • Explain the process of the gate opening and closing as well as following the voltage of the inner membrane

• to generate a membrane potential

• Membrane increases conductance (permeability for that ion), Na+ channels are open only for Na+

• Voltage gated channel

  • Resting MP, the channel is shut at -70 mV

  • Depolarize (less negative inside the cell) to open the channel! Depolarize to about -55 mV to open and close two types of gate

    • Activation Gate opens to allow Na+

    • Rapid depolarization

    • Inactivation Gate closes and Na+ entry as well as rapid depolarization

      • The gate is only removed once membrane potential goes back to threshold level (-55 mV)

Action Potential

• main definition

• Excitable definition for a membrane

• A short lived change in MP, used as a signal

• Can only be produced if there is voltage-gated Na+ channels in the membrane - therefore the membrane is ‘exitable’

• Process

  • Na+ channels open, MP goes to ENa+ = 60 mV

  • Rapidly inactivates

• When Na+ channels closes, the restoration of resting MP is only due to the leaking of K+ through K+ channels (K+ moves from in to outside EC fluid)

Threshold

• What is the threshold for the action potential

• What is regenerative mechanism? (relates to Na+ channels)

• Stimulus required to have a minimum depolarization to induce regenerative mechanism for the opening of Na+ channels

  • Regenerative mechanism: depolarization causes Na+ channels open, Na+ to move in, depolarizes more which opens even more Na+ channels

All or None Principle

• quality of stimulus vs the magnitude of the potential

  • Name the two types of stimulus to results in a potential

  • What (name it) type of stimulus does not result in a potential

• Threshold and supra threshold stimulus will result in the same action potential magnitude

  • Subthreshold does not result in an action potential

Frequency Coding

• What is frequency coding

  • What does the frequency indicate about?

• To code the information about the intensity of the stimulus, it is done through the changes of frequency of AP

  • Greater stimulus = greater frequency

Refractory Periods

• What are refractory periods

  • What happens during refractory periods

• What are the 2 types of refractory periods

  • Draw a diagram of a refractory period

• When action potential is generated, the Na+ channels are closed due to the inactivation gate, however the two types of gates need to reconfigure to their original form for the membrane to be ‘excited’

• Types of refractory periods

  • Absolute RP: no channels are reconfigured and therefore no secondary actions potential

  • Relative RP: some but not all channels are reconfigured, the channels that are reconfigured are able to produce another AP right after

Depolarization Block

• How can we create a depolarization block

  • What is the purpose of this?

  • What is the voltage of a depolarization block

• Explain the process to create a depolarization block

• Keep the membrane depolarized, keep at 20 mV

  • This prevents the Na+ channels from undergoing reconfiguration back to its original state

• Process

  • Prevent the K+ channel from leaking K+ ions out of the cell

  • Destroy the gradient by introducing more K+ into the extracellular space (KCl injection)

  • Remains in absolute refractory state and membrane is in-excitable

After-Hyperpolarization

• What helps with hyper polarization

• What is the max voltage it can reach?

• More polarized due to the extra K+ voltage-gated channels which flow K+ ions outwards

• Even more polarized then resting potential

• Possibly repolarized to -80 mV

Impulse Conditions

• hint: What is impulsing

  • What occurs during the impulse

• Due to action potential, does the reverse of of the potential difference across the membrane (- inside to + inside)

• Source of the depolarizing current to the adjacent membrane and Na+ channels opened in the adjacent

• Therefore, AP propagates across the entire membrane/cell

Excitable Cells

• is there many or very few cells that are exitable?

  • Explain why

  • If not, explain what else they do? (recall all cells have membrane potential)

• Which type of cell is usually excitable and explain why

• What is the issue of action potential travelling long distances? (propagating)

  • Explain the solution (what is it called: hint: think of something that looks like an axon in real life)

    • What affects the speed of action potential

  • What two properties are useful to adjust to solve the issue

• Most cells are not ‘excited’ due to the lack of Na+ voltage-gated channels

• Don’t produce APs, instead conduct passive currents because their main goal is to not carrying a signal across a distance

• Only neurons with long axons will generate propagating action potentials

• Issue with propagating action potentials

  • Signals start to get weaker the longer the AP travels across the membrane

• Solution: 

  • Cable Properties

    • Length constant 𝜆 and will measure how quickly the potential difference disappear as a function of distance

    • Conduction velocity of an AP depends on the 𝜆

    • Main useful properties to increase 𝜆 (current or voltage)

      • Increase diameter to decrease internal resistance and the lost of voltage

      • Increase the membrane resistance to get less current leaking out

Length Constant

• what three factors define length constant

  • Which one is removed?

• What does the calculation results tell you? (1 correlation)

• If you were to change the value of the length constant, how would you, and why would you?

• What is the equation (hint: use the picture provided)

• Defined by the internal resistance, EC fluid resistance and membrane resistance

  • However EC fluid resistance removed from calculates as its not easily adjustable 

• Defined to calculate the the distance you can travel until the voltage drops 37% of its original value

  • Ideally, increasing 𝜆 is good so the depolarizing current travels a long distance

Myelination

• how do you increase conduction velocity (one thing)

  • Give an example in the nervous system

    • What is the places called when they are not mylinated in the nervous system

• what is the disease called that affects myelination? What happens in this disease

• Increasing membrane resistance the easiest way to increase conduction velocity

  • E.g. specialized ‘glial’ cells or Schwann cells assists the peripheral nervous system (for the central nervous system it is the oligodendrocyte) through this way by wrapping themselves 50-100 layers around the axon to form a myelin sheath to increase membrane resistance and prevent leakage of current between nodes

    • Nodes of Ranvier: places where the axon is not myelinated (myelinated in sections)

  • Issue: multiple sclerosis

    • The nervous system will attack the myelin and gets damaged

Saltatory Conduction

• What areas in the axon can produce action potential and why

  • What is this conduction movement called

    • For this movement, how far can it travel (in terms of the next APs)

      • What is the advantage of having this movement

• What type of membrane potential is happening in the areas that cannot produce action potential?

• Only axons that are exposed are excitable and can generate AP because only those areas are where the exposed Na+ channels are, in between are not generating AP

  • Known as the jumping mode of conduction

  • One AP can generate APs for the next 5-10 nodes to -55 mV

    • 10th node of each section will serve as the depolarizing force for the next 10

    • **note that even if the first 2 nodes are damaged, AP can still travel to the next healthy node or unmyelinated axon (doesn’t stop the track)

  • Between nodes is passive currents

Unmylienated Axons

• What is the disadvantage of this

• What is the advantage of this

• Which wins for most axons?

• What is a remak bundle?

  • What type of glial cell can do this

• Bad because

  • Lots of current leakage and slows down conductance velocity (speed of conductance) due to small axon diameter and low membrane resistance

• Good because

  • Lots of Na+ and K+ are found in these area

• Overall: many axons are unmyelinated

***Remak Bundle AXON IS STILL surrounded by schwann cell and oligodendrocyte but on only for insulation and no winding

Axon Terminal

• what happens to the membrane potential conduction at the exon terminal

  • Why doesn’t it go backwards (recall what is required for the next AP)

• Conduction ends at the axon terminal

  • Reason it cannot go backwards: the Na+ channels are still inactivated during the refractory period so the current just dies out

Synapses

• Give the main definition

• Only list the two types of synapses

• Functional association of a neuron with another neuron or effector organs (muscle/gland)

• Types of synapses

  • Electrical

  • Chemical

Electrical synapse

• What are they known as

• How far apart are neighbouring membranes

• What are they bridged by and what is their function (what is transferring in between the membranes (2 types))

• Known as gap junctions

• Adjacent membranes 35Å apart and bridged by Connexins transmembrane proteins allowing small ions and depolarization to cross

Chemical Synapse

• What is transferring in between the membranes

  • What is the membrane called that releases it

  • What is the membrane called when it receives it?

• How far apart is the neighbouring membranes

• Explain how the transferring in the chemical synapse works

  • 3 steps

  • Explain why this doesn’t always work? Give statistics

• What is being prepared before chemical synapse transfer occurs

• Transmitter released between the EC space between membranes

  • Presynaptic membrane: Where the membrane released the transmitter and the surface is known as the bouton containing the vesicles

  • Post Synaptic Membrane: receives the neurotransmitters through binding with the specific protein receptors located on this membrane

• About 200 Å apart

• Processing station

  • Boutons filled with vesicles of neurotransmitters

  • Once the terminal gets depolarises the voltage gated Ca+ channels open and allow Ca in the terminal and the depolarizes the cell to -50 mV; this trigger the exocytosis (can be either kiss or run or full exocytosis) of the vesicles synaptic contents and these will bind to the postsynaptic cell

  • Binding of the neurotransmitters will trigger a response in the cell

  • **releasing vesicles are only probabilistic: 1 AP will have a 10-90% chance to releasing neurotransmitters

• Vesicles are already lined up with the presynaptic surface with the help of SNARE proteins located on the cell’s membrane

Post-Synaptic Receptor

• What is this receptor? Where is it located

• What happens when the neurotransmitter binds to it?

• Why is the receptor more important than the neurotransmitter?

• List two types of receptor effects

• Neurotransmitters diffuse and bind to the receptor protein in the postsynaptic membrane which then changes the shape of the protein

• ** the receptor are responsible for what happens or the effects, not the neurotransmitter (that why we can have different neurotransmitter e.g. man made to do something)

• Types of receptor effects

  • Ionotropic effect

  • Metabotropic effects

Ionotropic

• *____ binds to ____

• Types of *___

  • four types

  • Are they only limited to ionotropic things?

• What is post-synaptic potential

  • How long is this potential about?

  • Two types of PSP (two types of ions for each)

• Give an example (hint: nicotine)

• Ligand binds results in opening of an ion channel

  • Types of ligzands **all these ligands can also bind to the metabotropic receptor (this is why it’s very important to know that the receptor is what effects everything)

    • Ach: Acetylcoline

    • Glutamate

    • GABA

    • Glycine

• Post-Synaptic Potential: Because of the opening of ion channels results in the change of the post-synaptic membrane potential

• Time: 20-40 ms (as long of the neurotransmitters are still there)

• Specificity

  • EPSP (excitatory): for depolarizing (Na+, K+)

  • IPSP (inhibitory): for hyperpolarizing (K+ or Cl-)

• E.g. nicotinic receptor for Acetylcholine (neurotransmitter)

Metabotropic

• Main definition

• __ binds to ___

  • Explain what happens after the binding (2 possible things that could happen)

    • Give the types of things released for the 2nd type

• Types of ___ (6 kinds)

• Explain one specific neurotransmitter and effects (B-Adrenoreceptor)

  • What is it commonly used for

• (initiates a metabolic cascade to activate an enzyme)

• The ligand binds to the receptor, then activates the enzymes that is G-protein coupled

  • Types of ligands

  • ACh: Muscarinic receptor

  • Peptides: B-endorphin, ADH, substance P

  • Catecholamines: noradrenaline, dopamine

  • Serotonin

  • Purines: adenosine, ATP

  • Gases: NO, CO

• Enzyme either increases production or destroys 2nd messengers (to the next enzyme)

• 2nd messengers then activate other enzymes

  • **********cAMP, cGMP, InP3

• Example: phosphokinases will phosphorylates membrane protein and other proteins which will modify their ion currents

• Example of metabolic receptor and their effect: B-Adrenoreceptor

  • Neurotransmitter: Noradrenalin (NA)

  • Activates adenylyl cyclase through the G-protein alteration

  • Increase production of cAMP

  • cAMP activates kinases that phosphorylates Ca++ chanell

  • Increase Ca++ influx

  • Commonly for beta-blockers (help heart muscles and increase contractility)

Main difference between two effects (ionotropic vs metabotropic)

• Speed of effect

• Membrane potential

• Change of membrane potential

Spread of PSP

• when does spread of PSP occurs

  • In what are of the neuron does it occur in?

• What does it not generate

• Where does PSP go to?

  • What is this area called?

• Generated in area with a lack of voltage-gated Na+ channels (inexcitable membranes)

  • Neuronal dendrites and cell bodies

• **do not initiate an AP, only generates passive conduction

• Will travel to the nearest excitable membrane Trigger Zone (at the beginning of the axon)

PSP Summations

• Why do we have PSP summations (what is the issue if we did not have this?)

• What are the two types of summations?

  • Explain each type and how they can create AP

• The loss of current/potential before reaching the trigger zone

• Types of summation

1. Spatial Summation

• Multiple synchronous EPSPs all reach the trigger zone at the same time to create a suprathreshold

2. Temporal Summation

• Strong EPSPs and last about 30-40 ms before dying out

• Successive input (not all at once) on any synapse generates subsequent APSES that add on to pre-existing EPSP that, within a short period of time (e.g. 10 ms apart), can sum up to create a AP

Inhibitory Post-Synaptic Potential

• where is it located?

  • What is the advantage of the location

• In which cells is it more commonly found in and why would it be important there?

• Explain the process of inhibiting the PSP/AP

  • 3 steps

• Located at cell soma (cell body) found halfway between the site where EPSP in generated and the trigger zone

  • Advantage of location on the soma: the shunt (divert) the EPSP current away from trigger zone and out of cell

• Found commonly in the nervous system and more important than EPSPs

• Process

  • All IPSP have a Cl- channel

  • Equilibrium potential of Cl- is the similar to resting potential

  • Depolarization of the membrane results in the repolarization by Cl- channels back to -70 mV (inhibitory effect by preventing depolarization and excitation)

AP Spike Train

• How long does it last

• When does an AP spike train occur (what type of stimulus)

• Steps to generate the AP spike train

• What are the requirements for a spike train (1 things and where it must be located)

• Powerful synaptic input that can last up to 500 ms

• Very powerful inputs requires a continuous stream of APs (Spike train) to code for it

• Process to generate a AP spike train

  • After depolarization, the voltage-gated Na+ channels remain inactive (refractory period)

  • Right after each spike must immediate hyperpolarize the restore the channels back to its original state and overcome depolarization block

• Requirements for spike train

  • K+ channel must be located at the trigger zone to cause hyperpolarization and reconfigure the Na+ channels back to original state

  • This way the MP will shoot back immediately

Receptor Potential

• Main definition

• Explain the process

• What two things happen after a receptor potential

  • First type

  • For the second type pls explain what happens for the amplification (2) and the process (6 steps)

• Definition: a change in the membrane potential due to an external sensory cue signal

• Process

• Generally causes depolarization as it reacts with membrane proteins

  • Then depolarizes the sensory receptor upon the receipt of a specific energy (signal)

  • Exception: a receptor that hyperpolarizes (e.g. photoreceptors)

  • Receptor protein located in sensory cell membrane

    • Will change shape when a specific energy is received

• What happens after change of protein shape

1. Directly open ion channels

• Depolarizes the membrane by opening cation channels

2. Enzyme is activated via G-protein coupling

• Increase the produce of 2nd messenger which amplifies the signal

  • Stages of amplification of just one stimulus

1. G-protein activates number of diff enzyme molecules

2. Each enzyme molecule produces lots of 2nd messengers (cAMP)

• Summary: just one stimulus creates many messengers

• Process

  • Binding of chemical stimulus to a metabotropic receptor

  • Activation of G-protein

  • Activate enzyme adenyl cyclase

  • Production of cAMP - 2nd messengers

  • cAMP activate kinases

  • Kinases interacted with ion channels or phosphorylates other proteins

Olfactory Receptor

• what binds to an olfactory receptor

• Explain the process that causes depolarization

  • Explain what must also happen for an AP to work

• Receptor proteins binds to a specific odorant

• Process

  • Odorant binds to the specific receptor to activate the G-protein, G-protein activates the adynyl cyclase, production of cAMP, cAMP binds to ion channels to allow Na+ and Ca++ inside, depolarization of the membrane

  • The passive current must reach towards the trigger zone

Sensory Cell Transmission

• Only state the types of transmissions that can occur in a sensory cell

• generates AP

• releases vesicles when depolarizes

Sensory cells generate AP

• where is the start of the occurance

• Where does the AP go?

Excitement occurs at the point of branch, Receptor potential must travel and generate summation to the trigger zone to get action potential

Sensory cell releases vesicles when depolarizes

• What does it not produce, instead what does it do?

• How does this process work (explain the involvement of a cation channel)

• what is an example receptor that does this

• The depolarizing current won’t produce action potential

• Instead the current will depolarize the membrane enough to cause the influx of Ca+ ion through the Ca+ channels and trigger the exocytosis vesicles to release contents in the sensory cell

• E.g. Taste Receptors

Adaptation

• main definition

• State and explain the two main types

  • What occurs in both

  • What the main purpose of each type of adaptation (what kinds of changes in stimuli are the body interested in?)

• Adaptation: the membrane potential the decaying over time even though the stimulus intensity is the same

• Types

1. Slowly adapting

• The receptor potential is sustained during stimulus but is only interested in any overall changes in magnitude of stimulus

2. Rapid adapting

• Receptor potential elicited by the change in stimulus energy and decays to zero when constant

• Very interested in the velocity of the stimulus being delivered

Habituation

• main definition

• Do all cells have this?

• the response to successive stimuli in time

• Def: when repeated identical stimuli occurs, will elicit weaker responses each time

  • Depends on the cell if they do this or not (degree of habituation)

Coding of Stimulus Intensity

• How is the intensity of the stimulus coded: recall prev lecture slides

• What is the limitation of this

• How is the limitation overcomed

• Receptor potential (initial) will vary depending on the intensity of the stimulus

  • greater stimulus = greater receptor depolarization = more transmitters released or higher AP frequency and faster the membrane is brought back up from hyperpolarization

  • The frequency of AP (Impulse frequency) limited to the refractory period

• Solution to being limited by the refractory period

  • Include more higher threshold sensory neurons (require higher thresholds) for greater stimulus

Post Synaptic Receptors

• What are the two methods to determine the intensity of the simulus, based on the previous flashcard

• Methods to determine the intensity of the stimulus

  • Increasing frequency of AP from receptor A at the excitable membrane indicates stronger stimulus

  • When the stimulus strength continues to increase, add another receptor B with a higher threshold

    • Different receptors indicate the intensity of the stimulus (e.g. receptor A is lower intensity and receptor B is higher intensity)

    • Very useful if limited by the refractory period

Coding for Modality

• What is modality of a stimulus?

  • One modality = mutliple ___

• What is the main issue for coding for modality?

• What is the solution (what is this solution called?)

  • What is another kind of solution (how are the two solutions different from each other?)

• Coding for modality = the quality of the stimulus

  • One modality = multiple stimulus qualities

  • Issue: many diif receptor to indicate quality is difficult

  • Solution: Population Code

    • The ratio of activity from a limited number of receptor types (receptor types = population of receptors)

• Labelled line strat

  • The specific activity in one pathway indicates the quality ONLY = level of response

Receptive Field

• main definition of a receptive field

• give an example with the cutaneous sensory neuron

  • Types of receptor fields you can find in this type of sensory neuron

• Receptive field: Each sensory neurons responses to a particular area (e.g. a patch of skin)

  • That field is where you can activate that specific neuron

  • Every sensory neuron have their own receptive field

  • E.g. cutaneous sensory neuron has receptive field of the skin territory

    • 10-20 mm across for each neuron

    • Smaller secondary receptive fields found in more sensitive areas in order to have more specific location determination based on stimuli - two point discrimination

    • Larger secondary receptive field results in stimuli perceived in one point - no two-point discrimination

Blood Brain Barrier

• What is the purpose of a blood brain barrier

  • How is this done?

• What is the three key components of the BBB

• What disease and a type of drug causes the BB to break down

• When is there a purpose of not having a BBB

  • Purpose + Two example

• Brain and spinal cord must be protected from the outside circulation and body

  • How?

    • By controlling the ionic composition outside the neuron’s extracellular fluid space through Blood-Brain Barrier

      • No random neurotransmitters around

      • Avoid stopping AP (e.g. injection of K+ ions to prevent K+ ions leakage from the membrane)

• Two key parts and with blood capillaries

1. Fluid Bathing Neurons

2. Fluid in Ventricles/Cerebrospinal Fluid

• E.g. of unhealthy BBBs

  • Parkinson’s disease

  • MSGs

• Lack of blood brain barrier

  • Purposes: for the interactions with the endocrine system or require sensitivity to metabolites (chemicals and other things) in plasma (liquid part of the brain)

  • E.g. the hypothalamus require different kinds of hormones to function =  no BBB

  • E.g. circumventricular organs around 3rd ventricle have neurons needing to sense different chemicals = no BBB

Brain Encasing

• Three main parts

  • Two parts only list

  • last part has many different membranes, please state all

    • 4 main membrane parts

    • 1 main area name as well (what is in it and why it is important)

  • Talk a little about the blood vessels and how molecules can pass through

• Skull

• Meninges (parts)

  • Dura Mater (tough membrane, sac like containing brain and spinal cord)

  • Arachnoid membrane (delicate membrane)

  • Pia mater (membrane directly on top of brain)  that is tethered to arachnoid by arachnoid (memorization tip: spiders - pic looks like it) ‘Trabeculae’

  • Between pia mater and arachnoid known as the subarachnoid space have fluid CSF to float brain and prevent mechanical stress

    • Subarachnoid space has

      • Blood vessels > capillaries to the brain tissue > BBB (between capillaries and brain tissue)

      • Endothelial lining of the blood vessels has fenestrations (large gaps/pores) so that molecules can pass except for the brain (molecules SHOULD NOT PASS unless through the BBB) 

• Reticular Formation

Ventricles

• What are ventriles and what are the filled with

• State all ventricles found in the brain and the order in which contents are moved

  • Four parts

    • Addition 2 area names it goes through

• How is draining CSF done?

  • Where does it go?

  • What is arachnoid villi?

• ventriles: cavities deep inside the brain

  • All filled with cerebrospinal fluid

• The parts (in each hemisphere) and process of contents moving

  • Lateral Ventricle (LV) paired across the midline

  • Release contents into 3rd ventricle (located in the middle of the brain under hemisphere)

  • Communicate via “Aqueduct of Sylvius” to move content to the 4th ventricle

  • 4th ventricle contents moves in the “Central Canal” (found in the center of the spinal cord)

• Draining CSF

  • CSF goes to the ventricle in the central canal

  • Moves to the outer parts of the brain and exists at venous sinuses located at the midline to be drained

  • Arachnoid Villi: where the CSF drains into the venous sinuses/system

    • Pouching out of the arachnoid tissue, through the dura mater, into the venous sinuses so the CSF is drained there

CSF

• What is it

• What is it produced by

  • Main thing produces it

  • Secondary smaller part that produces it

• Where is CSF in?

• Where does it all go afterwards and to where??

• Compare CSF contents with blood contents

  • Two things that are similar

  • Two things that are different

• Total volume of CSF and how it is distributed among 2 parts

  • 1 part has two subparts

• How is CSF diagnosed

• From plasma that is produced by the ‘choroid plexus’ which lines all ventricles

  • However some is produced in the capillaries in the brain

  • Choroid plexus is made up of epithelial cells connected by tight junction

  • Has a network of capillaries ballooning out into the ventricular wall

• All ventricles filled with CSF

• All CSF eventually drained by the venous sinuses

• CSF continuously produced a day for cleansing (550 ml/day)

• Comparing with bloods

  • Same Na+ concentration and osmolarity

  • Reduced Ca2+ Mg2+ and K+ concentrations compared to blood

• Volume: total avg is 215 mL

  • Cranial CSF: 140 ml (115 ml subarachnoid space > 25 ml ventricles)

    • More in subarachnoid space to serve as cushion = most important function

  • Spinal cSF: 75 ml

• Diagnostic/therapeutic: lumbar puncture (spinal tap) to collect sample of CSF

Astrocytes

• What is it a type of

• Where is it typically located and function for neurons (location indicates purpose)

• How does signalling of neurons involve astrocytes (explain the process)

  • Has four main steps (one of them is a specific function the astrocytes does)

• three main functions

  • One function is very specific; explain why it does this well and the process

• What is latching?

• Astrocyte is a type of glial cell

• Capillaries are plastered at astrocytes feet that allow as a bridge between the capillaries and neurons

• Process of communication for signalling of neurons

  • Blood vessels have glucose

  • Goes through the blood-brain barrier to the astrocyte

  • Astrocyte does efficient glycolysis to produce lactate

  • Lactate is a starting material (substrate) for ATP production

• Functions of astrocytes

  • Removing neurotransmitters

  • Produce energy substrates (lactate) for neurons

  • Regulating Blood flow

    • Due to already being a bridge between the neurons and blood vessels can indicate when to constrict or dilate blood vessels

      • detect neural signalling increasing at the synapse and send their own metabolic signal outward to the blood vessels to tell about the increased activity level

    • Process

      • Glutamate in synapses trigger the Ca2+ release in glial cell, the wave of increased Ca2+ travels to the end-foot and triggers prostaglandin (PGE2) release (prostaglandin causes vasodilation = more blood flow)

• Latching

  • Following to latch on to blood vessels

  • Feet either latches on the blood vessels or the neurons to create the bridge