Vet physiology lecture package #1
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What is a solute?
its physical state changes when it is dissolved in solvent. ex) Na
What is a solvent?
a substance into which a solute dissolves ex) water
When concentration is higher on one side of a semi permeable membrane do we see only movement in one direction?
No while the net flow will go to one side the individual fluxes will go in both directions just from random movement of molecules
Does the solvent always have to be in higher concnetrations than the solute?
No not in super saturated solutions
What is ficks law?
Diffusion rate = diffusion coefficient * areaof membrane *concentration gradient
What is a colligative property?
property of a solution that is determined by the number of particles rather than by the kind
Describe % in units of concentration
What is the osmolarity of a red blood cell?
What does a solution need to be used as a fluid replacement?
- non permeable (otherwise cant do job) and same osmotic concentration
What is osmosis?
Net movement of water caused by a concentration difference for water moving across a membraner
Why does a fluid replacement solution need to benon permeable?
If it is instead of moving the water it will move the solute
gradual dispersion of dissolved molecules from regions of higher concentrations to region of lower concentration
- the effect osmotic pressure with respect to a selectively permeable membrane
- Based on the membrane and its permeability, more of a biological property
number of mole per litre of solution
Is tone a colligative property?
in an electro chemical gradient what 2 factors dictate flow?
Charge and gradient
if a solute diffuses through a membrane roughly how much tonicity does it add to the system?
number of moles of solute per kg of solution
Number of moles of osmotically active solute per litre of solution
Define osmolality? (trick question)
number of moles of osmotically active solute per kg of solution
What is an equivalents solution
- Total valence (absolute charge) * moles of solute per litre of solution
- absolute charge * moles
when putting a solution in blood you want it to have what to make it not change water movement and wreck red blood cells?
same amount of active osmolarity particles that cannot diffuse to keep the tone similar
Define isotonic, hypotonic, and hypertonic
- iso = equal osmotic concentration
- hypo = lower osmotic concnentration
- hyper = higher osmotic concentration
If a RBC is put into a hypotonic solution what will happen
water will flow in to even out the osmotic concentration and it could burst
3 main general things that make up biological membranes?
- double aphipathic lipid layer
cholesterol serves to do what in the membrane?
Stiffen the cell membrane
is the lipid bilayer static?
NO its quite dynamic and involves a lot of lateral movement however not a lot of movement out of the plane
if cholesterol stiffens animal membranes then what type of animals would it be really useful for?
Animals in very hot environments could use it to keep membranes stiff
oligosaccharide chains found on membrane proteins are essential for what?
Communication and recognotuion
The fluidity of the membrane allows for some important features such as
- Rapid migration of proteins along the plane
- Allows cells to change shape
- Allows lipids to constantly change places
4 functions of biological membranes?
- regulate movement of substances
- maintain position of enzymes in array (ex electron transport chain)
- Electrical signalling through ion movement
Describe where (outside or inside cell) there is higher concentrations of these ions
- Sodium = outside
- Pottasium = inside
- Calcium = outside
- Chlorine = outside
- Protein anions = inside not really anything outside
Why would we assume chlorine needs to be outside of the cell?
To maintain electrical balance with the other ions
Why must calcium be kept really low in the cell?
Can cause cell death
The donnan equation works on the theory of
Describe the donnan equation
- The concentrations of ions on one side of the permeable membrane must be equivalent to the concentrations on the other side, if not then there will be shift from equilibrium
- (y)1 x (R)1 = (y)2 x (R)2
What happens to a simple donnan situation (see page 7 of 1st lecture package) if you add a negative impermeable ion to one side
Since it cant move over on its own like other ions it will move other ions to equal out the electro and chemical forces within the system, since it is negative it will repel more negative charge and attract more positive charges
As well some water would move in to balance out the osmotic pressure
Factors important to why donnans equation applies to cell membranes?
- Anionic salts on impermeable intracellular proteins ust be balanced by intracellular cations
- These anions would create situation like the donnan equilibrium except cell membranes are actually slightly permeable to these ions, and this permeability would cause ion loading inside the cell and osmotic lysis
The osmotic disaster would be avoided because sodium and calcium continuously pumped out of the cell which gives the same effect as sodium and calcium impermeability, and thereore true equilibrium is never reached
READ PAGE 7 ON THE DONNAN EQUATION
Know what the general format of the donnan equation is and that it requires
- Both a positive and negative on each side
- Anything on both sides of the equation must be permeable
4 types of ion transport? describe them
- Passive diffusion - diffusion through membrane
- Passive transport - transport through channel or pore down electrochemical gradient
- Primary active transport - ATP driven active transport against chemical gradient
- Secondary active transport - active transport against electrochemical gradient driven by ions going down their gradient (often paired with primary)
Passive movement is always moving ____ a gradient
Passive transport is also called
3 different kinds of facilitated transport?
What is faster membrane diffusion or transporter?
4 characteristics of transporters
- Faster than diffusion
- Exhibit substrate specificity
- inhibitors for transporters are often known
Does passive diffusion ever saturate?
Do transporters run in reverse?
Active transport always requires?
In the sodium potassium pump what is added to the pump to make the sodium go out? is the bringing in of K+ the same?
- A phosphate groupe from ATP
- No the way back in is energetically favorable and spontaneous it involves spontaneous dephosphorylation
How can the failure of the sodium potassium pump cause cell lysis
First off forget the specific ions. The function of the pump is to keep gradients but also to maintain specific concentrations within the cell it normally kicks out more than it takes in, keeping the ion concentration within generally low when it stops the sodium leak channels continuously leak in more sodium causeing an osmotic imbalance which leads to influx of water and thus cell lysis
Which way do sodium and potassium leak?
Sodium leaks in potassium leaks out, the opposite way of the pump
If atp production stops what happens to the pump?
Shuts down, cell lyses
define ion channel. What are 4 features of them?
Class of proteins that traverse the cell membrane and conduct ions across it
- Mediate passive flux of ions
- High permeation
- Highly selective
- Can be gated
What are the four major gating signals in cells?
- 2nd messanger
- Mechano sensitive
Describe the general structure of a potassium channel
It has 4 sensors on its periphery and a pore in the middle, the sensos are what open the pore and either can be effected by drugs to be shut off
Describe the function, and speed for each of the channels
Calcium dependant potassium channel
- PL - resting membrane voltage, slow and steady, very constant
- VS- produces rising action potential phase, fastest channel
- VC - Slowly depolarizes and allows Ca into cell where it acts as a secondary messenger, Slow
- VP - Repolarizes cell to terminate action potential, slower than sodium faster than calcium
- CDP - Carries current that repolarizes cell following AP, slow and remains open if calcium stays too high, secondary effect of Voltage gated calcium
Does chlorine have a voltage channel?
Nope has different kinds of channels
What units is voltage in usually?
The resting membrane potential of the inside of a cell usually sits around?
-20 to -100
Excitable tissue can transmit information via two ways? Which is fastest??
During an action potential does the concentration of any ion within the cell change to a great extent?
No remember that the action potential happens very near the membrane, the concentration of these ions withijn the entire cell is far too great and outweighs the ability to change this is why you never run out of sodium ions...
What two factors contribute to the cells negative resting membrane charge?
Higher permeability to potassium in leak channels and a overall negative charge given by the sodium potassium pump
What is the cell more permeable to potassium or sodium>
If the pump stops what will slowly happen to the charge inside the cell
It will gain and become more positive giving it less potential to depolarize, this is because leak channels will slowly equiliberate everything
Is the equilibrium potential of ions unique to every ion or is it general?
Unique to every ion
Define equilibrium potential of ions
- point at which net flow across the membrane is 0
- point at which energy from electrochemical gradient equals energy produced by the charge on the membrane
- ALL IONS STRIVE TO MEET EQUILIBRIUM
So when an ion reaches its equilibrium what happens to its movement? Would we expect the equilibrium for Na to be + or -? What about potassium? Chlorine?
- It stops
- + cause flows in to make positive
- - cause flows out to negative
- - cause flows in to make negative
Is the equilibrium for an ion the same in all cells?
No different for every cell and every species
SEE PAGE 13 GOOD PRACTICE QUESTION FROM WEBER
ALSO MAKE SURE UNDERSTSAND CHART AND EQUILIBRIUMS OF IONS
Why do we often ignore chloride in movement of ions in cells
Its already super close to its equilibrium in resting cells
Which ion (Na/K) is farther in their equilibrium potential to resting cell membrane potential?
Do resting cell membranes have a high permeability to sodium?
- if it did it probably wouldn't be able to get such huge equilib potential and hold energy
Why does the Nernst equation always predict more negative when you use potassium to predict its membrane potential? What are 2 flaws of the Nernst equation?
- Cause only takes into account 1 ion and forgets small amount of positive Sodium leaking in
- Does not account for differences in permeability to different ions or change in permeability
- Can only account for one ion at a time
Because chlorine equilib is so close to the chlorine potential does it have much drive to go?
Nope that's why we don't take it into account when calculating membrane potential so tiny
During our example of the goldman-hodgkin..... equation we flipped chlorine ratio around, why was this?
To simplify and make it positive because it is a negative ion
Why would death by potassium injection be so painful?
Would fire all your muscles and cause convulsions essentially
The Nernst equation can model the relationship between potassium concentration and membrane potential when and when not?
At super high potassium concnetrations it works but at lower levels it falls apart
What equation works at physiological levels of K+ concentration and lower?
If K+ causes depolarization why would we ever supplement with it?
Cause it can be lost through the use of diuretics and needs to be mnaintained
Define , depolarization, hyperpolarization and action potential
- Depol = Vm becomes less negative than resting membrane potential
- Hyper = Vm becomes more negative than resting membrane potential
- AP = Large brief self propagating change in Vm, can travel long distances without decrement
We know that action potentials don't weaken over a distance, why is this so important?
Cause there are some long axons (giraffe neck) and if they weakend out the message would never make it
What is threshold potential? What occurs after an action potential?
- The level of potential that must be met to actually stimulate an action potential
As soon as a stimulus hits the threshold potential there is a change in the membrane as it goes from what to what?
Passive change to active change
Is threshold potential a constant property?
No it varies from cell to cell
So a stimulus activates a membrane, and doesn't reach threshold, is this active or passive change in membrane potential?
With passive change in membrane potential the bigger the stimulus has an effect on the membrane response. (T/F)
True but not in active change
At stimulation of an action potential what happens to the permeability for sodium?
Is depolarization similar in time in all cells?
No varies widely
Dendrite of a neuron receive input passively or actively?
Where does active generation begin?
Are all signals to the neurons dendrites excitatory?
No some are inhibitory, they simply subtract from the excitatory effects of other signals
inhibitory neurons do what to another neurons dendrites? What about excitatory? Are signals in the dendrites addable or are they all or none like in the axon?
Does passive depolarization move in one direction or many? What about active depolarization?
Why does active depolarization of a membrane only move in one direction
Cause it involves the use of voltage gated channels which have refractory periods to reopening
What is the soma of a neuron? the presynaptic terminals?
- The cell body
- THe axon terminals of the presynaptic neuron having effect on the dendrites of the post synaptic neuron
So while the action potential is spreading down a neuron it cannot go backwards because the channels immediately behind it are refractory but what about channels a distance beghind it? Couldn't the positive charge inside the cytosol travel back and activate those?
The charge within the cytosol traveling would now be considered passive change and would phase out over that distance, the active change is only on the membrane where the channels are located.
SEE PAGE 19 GOOD FIGURE TO UNDERSTAND WHY AP CANT GO BACKWARDS
3 traits of an action potential
- All or none
- Self propogating
- Ends spontaneously
Distinguish between absolute refractory and relative refractory
- Absolute occurs for a short period of time directly after AP and is when no depolarization can occur whatsoever because the voltage gates are not out of refractory yet and there is not enough out of refractory to make an action potential
- Relative is directly after the absolute and lasts a bit longer this is when many of the channels are still refractory but there is enough of them reset that if a large strong enough stimulus comes along it can get a crippled AP going
Are refractory periods caused by the resetting membrane potential?
No the membrane potential is reset it is the refracting sodium channels as well as the weaker sodium gradient due to recent depolarization
Is it possible to get a AP during absolute refractory period what if the stimulus is massive?
Why do we suppose the hyperpolarization is required in physiology?
To help reset many voltage gated channels
SEE PAGE 21 FOR POTASSIUM CURRENT SPEED VS SODIUM CURRENT SPEED
The function of the potassium current is too?
Repolarize the membrane
Because membrane potential is back to resting does that mean that the sodium concentration gradient is back to resting?
No because of the other ions affecting the membrane to bring potential back down the membrane is able to get to resting faster thn sodium
After action potential describe how the K+ and Na+ are out of equilibrium. What puts them back into equilibrium? Is this the only one of its kind?
- Excess Na just inside cell
- Inssuficient K inside cells excess outside cell
- Sodium potassium pump helps restore gradient
- No also Na/Ca pump in some tissues can assist
Does nerve myelination speed up conduction or slow it down?
Which speeds up an action potential larger diameter or smaller diameter? Why?
- Larger diameter axons will conduct impulses faster
- Because cell membranes are made of lipid which does not conduct electricity well. The smaller SA:V ratio therefore favors faster cytoplasmic conduction
Where myelination occurs there is no gated channels to the outside because it is covered? How then does it produce an action potential? What are these called?
- It will be able to hop from open space to open spacewhich will actually make the conduction faster than normal
- These are called the nodes of ranvier
What is salutatory conduction?
It is conduction along an axon when the impulse skips the myelin and hits only the nodes of ranvier
Is there often single neurons connecting to eachother alone?
No very rarely maybe in a reflex arc but often it is more of a web
Passive electrical conduction is (proportional/ unproportional) to its stimulus while active conduction is (proportional/ unproportional) to its stimulus
Active electrical conduction starts where?
Passive conduction is proportional to what 2 things?
Are neurons actually connected?
No they are separated by synapse and never actually connect
What is the purpose of inhibitory neurons?
To be able to cease movements or doing things as well as to b able to have restraint
Would you expect the stimulus going through the soma of our typical neuron to be larger the same or less than the intensity needed for our action potential? Why?
Larger because if passive stimulation weakens over distance then our original stimulus must be larger than our threshold to actually activate our threshold by the time it transverses the cell body
Describe an EPSP and IPSP
- Excitatory post synaptic potential - when a presynaptic neurons stimulation on the post synaptic neuron has a depolarizing effect
- Inhibitory post synaptic potential - when a presynaptic neurons stimulation on the post synaptic neuron has a hyperpolarizing effect
Is a cell body always in our typical spot that we see?
No cell bodies can be located in many places along the axon and in fact in many sensory cells it is located quite a ways down the axon and if the axon hillock goes with it it can take a very strong passive stimulus to activate an action potential
What are the two types of neural summation? Explain them thoroughly.
- Spatial summation - When two distinct neurons simultaneously sum their inputs on the post synaptic neuron because they are at the same time and SPACE
- Temporal summation - Successful rapid input from the same presynaptic neuron is electrically summed simply because its outputs are so close together the passive stimulation hasn't gotten away yet
What causes vesicles in the presynaptic neuron to fuse with the plasma membrane and expel their contents?
Not Na+ Sodium with the action potential opens up Ca2+ gates which will specifically move the vesicles towards active zones, the higher calcium concentration near the membrane cause fusion`
Do vesicles vary in the amount of neurotransmitter they have? What is this refered to as?
- No they have a very standard amount
- Quantal release means can count essentially how many vesicles released based on amount of neurotransmitter released cause it is so standard
What is the off signal for a neuron transmission stimulating the post synaptic neuron?
Removal somehow of the neurotransmitter from the cleft
Neurotransmitters bind onto what on the post synaptic neuron?
What happens with the membrane from the fused vesicles?
Recylced by cell
So fusion of the presynaptic vesicle with the plasma membrane is a 2 or one step process?
- 2 step
- Move toward active zone
- Fuse with membrane
When a vesicle is moving towards the active zone what is driving it and what pulls it to attach to the active zone? Which is probably activated by what?
- GTPases along the cytoskeleton or motor proteins
- Calcium likely
Once the vesicle is in the active zone what is the name of the protein complex that docks the vesicles to the membrane and eventually fuses it to it? What is required for fusion?
- SNARE protein complex
- An increase in Ca causes conformational changes in snare resulting in fusion
Botulinum toxin works by doing what?
- Cleaving snare and not allowing vesicles to fuse and exocytose
- Stopping acetylcholine release
So if there is a drug that prevents Na release it doesn't only effect the ability of the action potential to go but it stop what chain of events?
- Opening K+ channels
- Ca influx
- Vessicle fusion
3 fates of neurotransmitters in the synapse? Give examples of each.
- Enzymatic degradation within synaptic cleft - acetylcholine
- Reuptake - serotonin taken up by presynaptic transporters
- Diffusion - to a certain extent with every neurotransmitter
Which is the only mechanism of removal for peptide neurotransmitters in the synapse
What is the catch with diffusion being the way of removing neurotransmitters from the synapse
Slow therefore a long duration of action
Give 10 examples of neurotransmitters and their typical effects.
- Acetylcholine - fast excitation or slow inhibition
- Glycine - Fast inhibition
- Gamma- Aminobutyric acid - Fast and slow inhibition
- Glutamate - fast excitation, slow change in postsynaptic metabolism
- Norepinephrine - slow excitation, slow inhibition
- Dopamine - Slow post synaptic effects
- Serotonin - Slow excitation or inhibition
- Nitrogen oxide - Synaptic modulation
- ATP - Fast and slow synaptic transmission
- Histamine - Slow modulation
What does the effect of the neurotransmitter really depend on?
- The properties and state of the postsynaptic cell
- So no neurotransmitter is garunteed to do any specific thing
Describe fast chemical transmission vs slow chemical transmission across a synapse. Does it have anything to do with the rate of diffusion?
- Fast chemical transmission is when the post synaptic neuron has fast responding protein receptors (for example channels or transporters)
- Slow chemical transmission is when the post synaptic neuron has slow proteins which is when there is secondary messengers involved like in the case of G coupled proteins
No it has nothing to do with rate of diffusion which is constant
What is an advantage of having a slow chemical transmision
Ability to amplify message through multiple steps
What are the 2 G-protein linked receptor pathways? Describe them in depth and highlight the differences
- cAMP pathway
- Inositol phospholipid pathway
- cAMP = Signal -> receptor transduction - amplification - second messenger - internal regulator - tissue specific kinase specific effectors - cell response
Inositol phospholipid pathway = External signal -> reception, transduction - amplification - phosphorylated precursors - second and third messengers - internal regulators - tissue specific kinase specifc effectors - cell response
READ CAPTIONS ON PAGE 29 MAKE SUR EYOU GET THE OVERALL PICTURE
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