Theme 1 : Physiology Flashcards
Which ion is plasma mainly based of?
Na+
Why is plasma different to Interstitial fluid?
Lacks blood proteins (anions)
Name the characteristics of intracellular fluid
K+ based and has lots of proteins (anions)
Where can you find transcellular fluid? Can you give examples?
in the lumen of tubes and organs such as:
Cerebrospinal fluid surrounds parts of the brain, urine in bladder, chyme in GI tract
Primary active transport
moving solutes against their concentration gradient coupled directly to consumption of ATP and the result of respiration
Secondary active transport
moving solutes against their concentration gradient WITHOUT consumption of ATP but instead using the downhill movement of another ionic gradient (eg the transmembrane Na+ gradient) to power the uphill movement of the other solutes.
How is Na+ gradient is created and why is it classified as a secondary active transport system?
by respiration and consumption of ATP, so these co-transporters are Indirectly powered by respiration and ATP consumption.
Transporters.
membrane proteins that couple the transport of two different molecules so that both molecules go across the membrane together.
Are transporters passive or active?
It is a passive process, so at least one of the particles must be going down its concentration gradient
Exchangers
membrane proteins that couple the transport of two different molecules so that one molecule goes in while another goes out.
It is a passive process
Leak
a passive movement of ions across a membrane that may not include a protein to facilitate the process.
What do ions do
Act as second messengers
fertilise
muscle contraction
exocytosis
create energy
move water
activate enzymes
control transmembrane voltage
what happens if you have the wrong concentrations?
Cardiac arrhythmias
Tics/other nervouse dysfunctions
seizures
bone deformities
oedema
Causes of ionic imbalances in patients
Trauma and haemorrhage
Diabetes
Diuretics (non-K+ sparing)
Kidney dysfunction
hormonal imbalances
severe dehydration
vitamin d imbalances
extensive vomiting and diarrhoea
Voltage
It is the difference in potential energy between 2 points in an electrical field which is the electrical potential or driving force for charged particles (ions) to move
During an action potential, what is the most important concept?
Vm will change dramatically, yet the concentration gradients of the ions will remain virtually unchanged
What is the chemical force on each ion? Can you give an example
diffusional force
= Is based upon the difference in concentration ACROSS the membrane
E.g. If there is 10X as much Na+ outside than inside, the chemical force on Na+ channels is 60 mV directed into the cell
What is electrical force?
based on Vm (the membrane potential, which varies over time).
What is electrical force based of off?
This is based on a few positive charges being UNPAIRED with negative charges ON THE SAME SIDE OF THE MEMBRANE, so there are slightly more positive charges on one side of the membrane than the other
Net force =
chemical + electrical force
ONLY AT EQUILIBRIUM:
Chemical force = -1 x electrical force
Net force = 0
In a membrane, explain it’s electrical field initially
Electrically: At this point, there is no electric field across the membrane (because all positive charges are matches by negative ions).
However, the chemical gradients for both Na+ and Cl- are creating a force driving those ions inward
(Chemically more ions outside than inside the membrane)
What happens if 10 Na+ ions move from outside to inside, but no Cl- ions follow?
When positive ions cross the membrane, they leave behind negative ions.
Now there is a strong electric field across the membrane, which will push the Na+ ions outward but the chemical force on Na+ ions is virtually unchanged
What will the electric field created by the movement of Na+ do?
create an electric force that will affect K+ ions, Ca2+ ions, Cl- ions, etc
Physiology (3 key main points)
To explain and understand how living things work.
The study of function in the body
It is particularly based on physics, especially forces, pressures, electricity,
It considers systems and mechanisms
Pathophysiology
The mechanism by which a disease process causes the organ to fail
Non-physiological
Pathology or Lab
What is homeostasis of a system?
Persistence through change: the regulation of the cell’s or the body’s internal environment (extracellular fluid) so that it tends to maintain a stable, constant condition
Why (and when) physiology is useful in medicine?
Understanding what is happening in the patient, for making better cures, basis of therapeutics, the basis of anaesthetics and patient monitoring during surgery
Chvostek’s sign
one of the signs of tetany seen in hypocalcemia.
When the facial nerve is tapped at the angle of the jaw, the facial muscles on the same side of the face will contract momentarily
What is Hypocalcaemia?
(too little calcium in the plasma)
What are the consequences?
can be remembered as a disorder that causes too much activity:
arrhythmias, ECG abnormalities, over-reactive reflexes, and seizures.
What is Hypercalcaemia? What can it lead too?
(too much calcium in the plasma)
typically leads to too little activity such as constipation and psychological depression.
What is Paraesthesia?
an abnormal prickly sensation of pins and needles or of numbness
Where in the cell are levels of each ion maintained?
The cytosol
How is action potential driven?
There is ~10X more sodium in the extracellular space than intracellularly.
There is ~30X more potassium in the intracellular fluid than extracellularly.
There is a small amount more (60%) H+ inside the cell than in the extracellular fluid
keep in mind that there is much less free H+ than there is K+
What are excitable cells?
Cells that can propagate an action potential
Can you give 2 examples of excitable cells?
Neurons and myocytes (muscle cells) are excitable
Can you give 3 examples of non-excitable cells?
skin, liver, epithelial cells (e.g. gastric)
Most non-excitable cells WITH ion channels are… because….
epithelial
move lots of ions
So excitable cells don’t move ions long term, what do they do?
They move tiny amounts of ions to make signals
So, very few ions ever really move across the membrane
Tiny change of movement of ions
What do movements of small amounts of ions cause?
change of voltage, drive currents, or increase cytosolic Ca2+
What is the long-term function of excitable cells
Maintain a consistent gradient of ions
What happens after Na+ gets pumped through ion channels?
Cl- tends to follow Na+ (& other permeable cations)
Water follows Cl-
Which ion is the most concentrated in Plasma and why? What does this make plasma in terms of electric potential?
Highest in Na+ concentration (to balance protein anions)
Is slightly more negative in electric potential than the Extracellular Fluid (ECF)
What is the composition of cytosolic fluid? (4 things)
Highest in total cations
Highest in Protein
Highest in electrolyte concentration (milliEquivalents)
Most negative voltage
What is the composition of extracellular space? And why?
Highest Chloride concentration (lacks protein anions), not much protein is pumped out of the cell as protein concentration is highest in the cell
Lowest electrolyte concentration
What is the difference between plasma and extracellular fluid?
The main anion in extracellular fluid is mostly chloride (with a dash of other anions such as HCO3-), while in plasma, the anions balancing Na+ are a mixture of chloride and proteins.
Why is intracellular fluid highly negative?
a small number of negative ions (Cl-) are not paired with a positive ion (e.g. K+) because K+ tends to leak out without any anions following it.
Channels
membrane proteins that open and close and let a specific ion flow down its concentration gradient.
Open channels create a passive process, so ions only go down their concentration gradient
What are the conditions calcium must be in to be free to activate enzymes?
Ionized and in solution
What are the other forms calcium can be in?
- In bone, part of an insoluble solid that won’t react with enzymes
- Bound to proteins like calbindin so it will not react
- Sequestered (isolated) inside cellular organelles (sarcoplasmic reticulum)
How concentrated is cytosol in terms of free calcium?
Very low ~ 100 nanoM
What is the concentration of Ca ions in the cell? What does this cause?
There is approximately 10,000 X more free calcium in the intercellular fluid than in the intracellular fluid, so there is immense electrochemical driving force pushing calcium into the cell.
What can occur when there is high cytosolic calcium?
Muscle contraction
Cystolic concentration is the mediator of what process?
The action potential triggers muscle contraction
What are the rules of ionic balance?
The concentration of positive and negative ions must “nearly” balance
Any ion that leaves the cell must be replaced soon by another ion of that type coming into the cell
Energy is always being used to re-establish the ionic gradients across membranes to correct the leak
What is the pH of a cell?
The pH of the extracellular fluid (7.40 ± 0.05) is less acidic than in the cytosol (7.20, although this can vary based on the cell type).
How are changes in blood pH corrected>
actions of the kidneys (can make more acidic by secreting acid) and the lungs (can mak it more alkali)
Name the functions of Carbonic anhydrase
Creates acid
Creates base
Contributes indirectly* to process of H+ crossing cell membrane (& across epithelia)
Helps (indirectly*) to transport CO2 around body
Why does CO2 cross membranes and not H+ itself?
CO2 is uncharged and readily crosses the membrane
Why cant CO2 transport around the body? What does it do instead?
CO2 is poorly soluble in blood, must dissolve in a fluid (intracellular) therefore in the form of HCO3-
H+ and HCO3- are highly soluble
What is the chemical reaction that occurs to CO2 in many parts of the body?
CO2 + H2O -> H2CO3 -> H+ + HCO3-
State where Carbonic Anhydrase is used for Homeostasis in Many Systems? And for each state what it does?
Red Blood Cells: “Chloride shift” for removing H+ from muscle
Lungs: for eliminating CO2 source from blood
Gastric Parietal cells: secreting acid into stomach
Pancreas: secreting bicarbonate
What are Gastric pits and where are they found?
small projections on the lumen of the stomach
How do parietal cells organize themselves and why?
organise themselves invaginations = increases surface area
How do blood vessels supply fluids to parietal cells?
Through Basolateral membrane (outwards of parietal)
Apical membrane (in terms of parietal cell)
towards the gastric pits for parietal
What is the formula that forms in gastric parietal cells?
H2O + CO2 -> (VIA CARBONIC ANHYDRASE) HCO3- + H+
How are the reactants in the gastric parietal cells supplied?
From the blood via the interstitial space
In the gastric parietal cell, where will H+ be pumped to?
Lumen of the stomach via membrane protein on the apical side against it’s concentration gradient
In the gastric parietal cell, where will HCO3- be pumped to?
The blood via membrane protein on the basolateral side
Which protein pumps out H+? What replaces H+?
H+/K+ ATPase (Proton pump) , K+
What inhibits proton pumps?
Omeprazole
What protein pumps out HCO3-? What replaces HCO3-?
Chloride-bicarbonate exchanger (passive)
How does the parietal cell get rid of the K+ build-up?
Down concentration gradient by potassium channels back into the stomach or on the basolateral side toward the blood
How does the parietal cell get rid of the Cl- build-up?
Out the apical side, build up of HCl in the (lumen) stomach via passive chloride channels
K+ Depletion?
Maintained by Na-K pump
In excitable cells, Voltage (across membrane) is used to…
signal changes
In muscle cells, +20 mV means the cell wants to contract (i.e. “on”), while -90 mV means the cell wants to relax (“off”) *E
Ion movements across membrane are what determine voltages and currents
Define Voltage
the difference in electric potential energy per unit charge between two points
Define Current
a flow of electric charge through a medium (through a surface, esp. a X-section)
Define resistance
the opposition to the passage of an electric current; the inverse quantity is electrical conductance (g), measuring how easily electricity flows along a certain path
What is Ohm’s Law?
V = I × R
or I = V x g (g = conductance = 1/R)
What is Conductance?
how easily charge (e.g. ions) moves (eg across a membrane)
What is transmembrane potential (Vm)?
A measurement of the overall electrical potential energy across the membrane
What does Vm depend on?
Vm depends on the relative electrical currents and conductances of different ions
Fully permeable membranes will (generally) have a Vm of zero across them (e.g. death)
What happens when an ion channel in the membrane opens?
Current flow - The movement of charged ions
When electrically unmatched ions accumulate on one side of the membrane, that creates a change in voltage
When K+ ions leave the cell, they leave behind negative charges so that the cell membrane changes its voltage to become more negative inside
What is the difference between specificity and selectivity?
Specificity = the fact that Na+ channels (in theory) only conduct Na+ ions, especially by design
Selectivity = The comparative preference that Na+ channels have for conducting Na+ ions more than K+ ions. Selectivity is how the channels actually work. In fact, Na+ channels may conduct a tiny amount of K+, but in a mixture of Na+ and K+, the channels would conduct much much more of Na+.
What happens when Na+ channels open?
The membrane tends to become positive inside
= [Na+] is higher outside the cell than inside
The extracellular space of all cells is electrically joined and thus has the same voltage everywhere
= The extracellular fluid is considered the electrical ground
What happens when K+ channels open?
K+ flows from inside the membrane to the extracellular space the membrane becomes negative inside
[K+] is higher inside than outside the cell
When do Na+ channels start to open and close?
Na+ channels start to open when the inside of the membrane becomes more positive (i.e. > -55 mV).
But then stop conducting automatically after a time delay
Na+ channels close when the membrane potential is negative
When do K+ channels for repolarisation open?
When the membrane becomes positive inside
But these channels are slow, they open after a time delay
= This subset is called “Delayed Rectifiers K+ channels”
Why are there Delays in K+ Channel Gating?
if the Na+ and K+ channels both opened simultaneously, there would be an immediate increase in Na+ current going inward, but there would also be an immediate increase in K+ going outward, and the net effect would be essentially little or no current (instead of depolarisation).
The greater the permeability (or conductance) for the ion…
the more the membrane potential is driven toward the equilibrium potential for that particular ion
If one type of ion channel is much more conductive than all the others put together…
then the membrane potential will become (nearly) the equilibrium potential for that ion.
What is the difference between high permeability and high conductance?
High permeability indicates that particlemassmoves easily through a membrane.
High conductance indicates that electricalchargemoves easily through a membrane.
What is the equilibrium potential of sodium ions?
+60 mV
What is the equilibrium potential of potassium ions?
-90 mV
What is the equilibrium potential of calcium ions?
+123 mV
What is the equilibrium potential of chloride ions?
-40 mV
How do Open sodium ion channels control voltage?
If many Na+ channels are conducting but there are no other currents, the membrane potential (Vm) will go to +60 mV
How do Open potassium ion channels control voltage?
If many K+ channels are conducting, but there are no other currents, the membrane potential (Vm) will go to -90 mV
What happens to the equilibrium potential when both Na+ and K+ channels are open? (add conditions)
If both K+ channels and Na+ channels were open, and if the cell membrane was exactly equally permeable to Na+ and K+ (which is unlikely), the membrane potential would go to the average between their equilibrium potentials (i.e. -15 mV)
What happens during resting potenitial (terms of voltage)?
the membrane is negative inside
~ -70 mV for neurons, but it depends on the cell type
The membrane is more permeable to K+ than to anything else
What happens during action potential (terms of voltage)?
the membrane becomes positive inside (+20 mV to +60 mV) - mainly +40 mV
Depending on the cell type, the membrane becomes temporarily much more permeable to Na+, Ca2+, or both
Ca2+ channels or Na+ channels open
Describe what happens during Initial Depolarisation.
The cell starts at rest (-70 mV)
Something causes the cell to become less negative
Depolarisation: inside the cell the voltage becomes less negative (or more positive)
What causes the initial depolarisation?
Could be a nearby cell depolarising
Could be synaptic transmission where a neurotransmitter opens a ligand-gated channel
What happens If Vm remains below the threshold during the initial depolarisation?
Background K+ permeability pulls Vm back to -70 mV
This is a “failed initiation”
Describe what happens during depolarisation.
The initial depolarisation causes a few of the Na+ channels to open
Na+ permeability increases, Na+ current flows through channels into cell
The additional current of Na+ going into the cell = more depolarisation (ie the membrane potential moves closer to 0 mV)
This acts as a positive feedback loop
The positive feedback of Na+ channel conductance and voltage continues until the membrane becomes quite positive (> +30 mV)
What is the threshold voltage has to pass to commit to an action potenial?
-50 mV
Describe repolarisation in AP
Repolarisation = the voltage becomes less positive (or more negative) inside the cell
Due to the passage of time, 2 delayed-action events occur
Na+ channel inactivation = decreases in Na+ current going in
Delayed rectifier K+ channels open which increases K+ going out
These cause the membrane to be less positive and more negative inside
Describe what happens during after-hyperpolarisation
At the end of an AP the voltage inside temporarily becomes slightly more negative than at rest
Followed by a return to the resting membrane potential
During AHP: the increase in K+ permeability and decrease in Na+ permeability means the membrane potential moves closer to EK
What happens when after-hyperpolarisation causes refractory period?
new action potentials cannot be initiated
What are synaptic bouton?
aka axon terminals, synaptic boutons are small swellings that are found at the terminal ends of axons - bulby
What does action potential cause?
Calcium channels gate to open when Vm becomes positive inside during AP, and there is an increase in calcium ions in the cytosol
what does the change in voltage due to action potentials do intracellularly and extraceulllarly?
leads to other changes inside the cell:
Second messengers: Calcium, kinases, phospholipases
In Muscle: contraction
can lead to changes in other cells:
Synaptic Transmission
What is a neurotransmitter?
An endogenous chemical released extracellularly by a neuron which is used to Signal
To other neurons, myocytes, endocrine cells
Across a synapse
Under physiological conditions
What does endogenous mean?
naturally made by the body. This is the opposite of “exogenous”, which is something from outside the body, such as a a drug or toxin.
How are Neurotransmitters categorised by size & chemistry?
Small molecules : amino acids (glutamate), Monoamines (Dopamine) and Acetlcholine
Proteins, peptides and large molecules: Neuropeptides (substance P for pain)
What is Glutamate?
The main excitatory neurotransmitter in the central nervous system. It is an amino acid (small molecule) (i.e. one of the building blocks of proteins).
What is dopamine?
a neurotransmitter of the central nervous system associated with motor organization and motivation. It can be excitatory or inhibitory.
It is a small molecule that is initially synthesized from tyrosine (an amino acid).
What is substance P?
a neurotransmitter of the central nervous system associated with sensory signals of pain and stress.
It is a peptide (made of 11 amino acids linked in series) that is originally derived from a larger polypeptide/protein.
What is acetylcholine?
a neurotransmitter found in both the central and peripheral nervous systems.
It is a small molecule that is not related to amino acids.
Peripherally it is the neurotransmitter at the neuromuscular junction and in the autonomic nervous system. In the central nervous system it is important for alertness and memory.
Give an Example of neurotransmitter family
Catecholamines
Describe how tyrosine turns to adrenaline
tyrosine -> dopamine -> noradrenaline
which causes the Reticular activating system = a sparse set of neuronal circuits that runs from the brainstem to the cerebral cortex.
It is responsible for regulating arousal and sleep-wake transitions in the Locus coeruleus = a nucleus in the brainstem that is the origin of the reticular activating system.
-> adrenaline (for fight or flight)
Describe the lifecycle of a neurotransmitter molecule (8)
- Neurotransmitter is synthesised in cell body/ in terminal
- Neurotransmitter is packaged into vesicles
- The vesicle is transported to the cell membrane to be released
- Depolarisation of action potential causes Ca2+ channels to open
- Increased frew calcium causes vesicles to fuse with membrane
- Neurotransmitter is released when vesicles fuse
- Neurotransmitter binds to and activates postsynaptic receptors
- Neurotransmitter diffuses away and is metabolised and/or transported back into terminal
Describe the synthesis of a neurotransmitter
In the soma (cell body) or locally in the axon terminal
Sometimes instead of synthesis it is recycled:
Reclaimed from the synaptic cleft (after previous use)
How is neurotransmitters packaged?
Transported into a vesicle for storage
In some cases, a neurotransmitter is not packaged -
It will be released directly from presynaptic terminal
When are neurotransmitters released?
When presynaptic bouton is electrically depolarised
Vesicles previously filled with neurotransmitters fuse with membrane
= Triggered by an increase in cytosolic free calcium
What does activation of a receptor when the receptor and NT have a lock and key fit?
Typically open an ion channel
Some receptors cause the postsynaptic cell to depolarise, which may lead to an action potential *E
But some receptors do the opposite and tend to prevent the postsynaptic cell (which will have inputs from many cells) from having an action potential,
= Thus, some inputs to the postsynaptic cell are excitatory and some are inhibitory
How are NT removed from the synapse?
There are drugs that inhibit the enzymes that breakdown neurotransmitters, e.g. acetylcholine esterase inhibitors (AChEi)
There are drugs that inhibit the transporter proteins that transport the NTs back into the cell, e.g. selective serotonin reuptake inhibitors (SSRI)
Explain overall the Ionic Events in Skeletal Muscle contraction
ACh binds to its receptor
Small depolarisation
= Small amount of Na+ goes inward
Triggers Action Potential
Na+ goes inward, then K+ goes outward
(EC coupling)
Calcium Increases
2nd messenger
Moves Troponin/Tropomyosin out of groove
Myosin Interacts with Actin (Crossbridge Cycling)
Cleave ATP
Sarcomere contracts
What is the neuromuscular junction?
A specialised intercellular connection between a neuron and a muscle cell (myocyte)
What is the neurotransmitter for skeletal muscle?
Acetylcholine (ACh)
What eliminates ACh from the synapse?
acetylcholinesterase (AChE)
Where is acetylcholine synthesised?
In cytosol (both by soma, then transported to neuron terminal)
What happens when acetylcholine crosses the synaptic cleft?
ACh activates ACh receptors on myocyte membrane
Active ACh receptor causes a small depolarisation in myocyte membrane that may initiate myocyte action potential (i.e. excitatory)
Where is the Nicotinic acetylcholine receptor located?
On the myocyte membrane
What is the function of the sarcomere?
Sarcomere shortens by pulling fixed structures (Z lines) toward each other
which causes muscle contraction
What is the myofibre?
one long multi-nucleate muscle cell
What is myofibril?
organelle, string of sarcomeres
What does the A band contain?
M line (in H band) and thick filament with myosin
What does the I band contain?
Z line with thin filament with actin and also titin
What is myosin?
“the motor protein”
Single-molecule with:
long straight double helical tail
the double head region at one end
hinge or neck region between tail and head
myosin molecules aggregate with tail regions together to form thick filaments
Where are thin filaments pulled?
toward centre of sarcomere
towards the M line
Describe the cross-bridge cycle
Thin filaments are pulled toward centre of sarcomere (M line)
overlap between thick and thin filaments thus increases and Z lines of each sarcomere come closer together
I and H bands progressively get shorter with each sequential round of cross bridge cycling
width of A band never changes
Describe the structure of thick filaments
Many myosin molecules make up a thick filament
The center of each thick filament is bare zone = only myosin tails and no heads
Half thick filaments project from either side bare zone
minor proteins in bare zone keep parallel thick myosin filaments aligned
minor proteins constitute the central M band of A band
What are thin filaments anchored to, compromise, and overlap with?
Anchored to Z lines
Comprise I bands of the sarcomere
Also partially overlap with A bands
What are the 3 components that make up thin filaments?
Actin polymers
G-actin = glubular actin = a single polypeptide unit
to F-actin = filamentous actin = many G-actins aligned like beads on a string
Tropomyosin polymers - wrap around actin polymers
= Block actin-myosin activity
Troponin complexes
= Control tropomyosin
What are the 3 subunits of troponin?
TnI (I = inhibitory), which connects to the thick filament/actin
TnC (C = calcium), a regulatory subunit that undergoes a conformational change when it binds to calcium, and TnC also binds to TnT (and TnI).
TnT (T= tropomyosin) binds to tropomyosin, and can pull tropomyosin out of actin’s active myosin-binding site.
Describe the composition of actin in thin filaments
G actin – monomeric or globular form
Many G actin molecules polymerise into double helical strand:
The F-actin (filamentous actin) helix has a groove on each side
Groove occupied by tropomyosin
Troponin is attached to both thin filament & tropomyosin
What is Excitation-Contraction Coupling?
The link (molecular process) between:
The depolarisation of the membrane (with a tiny influx of calcium)
And the consequent huge increase of cytosolic calcium that then leads to contraction
How is a voltage change (AP) turned into a contraction?
Diffusion of free Ca2+ into the cytoplasm
What are the 4 classes of second messengers?
Ions (especially calcium, e.g. E-C coupling)
G proteins
Phosphorylation (or dephosphorylation)
Intracellular receptors (e.g. for steroids, which can cross the cell membrane)
What is the second messenger in muscles?
Free calcium
Where does most of the calcium come from?
From the sarcoplasmic reticulum (SR)
SR = smooth endoplasmic reticulum in muscle cell
Where large concentrations of calcium are stored; right next to the myocyte’s actin and myosin
Describe the direct physical connection between calcium channels of the membrane and calcium release channels of the sarcoplasmic reticulum
membrane depolarises
membrane calcium channels undergo a conformational change
SR calcium release channels = undergo a conformational change that opens them
Calcium flows from SR to cytosol
What is a twitch?
= a single contraction of a muscle fibre (between action potentials)
= When a series of action potentials stimulates contraction but the interval between them is long enough to allow complete relaxation in the muscle
What happens if the frequency of action potentials are high enough?
twitches fuse together in a process called summation
What is tetany?
A process whereby a myocyte continuously generates its maximal force for a duration lasting at least twice as long as a single twitch.
= continuous maximal contractile force and shortening
What happens to calcium during a twitch?
Calcium is pumped back into SR during relaxation
What happens to calcium during a tetany?
Relaxation is not long enough to pump calcium back into SR
There is an accumulation of free calcium in the cytosol
Thus, cell remains contracting despite the fact that Vm is repolarised
This state lasts for only a short period
Describe the duration of AP compared to a twitch of a muscle
Action potential is much more brief in duration than a physical twitch of the muscle.
There is a Delay between AP and force generation
What occurs in resting state of sarcomere in cross bridge cycling?
myosin heads are blocked from binding to actin by tropomyosin, which occupies the specific binding sites (in F-actin double helical groove)
What is cross bridge cycling?
The sequence of events underlying muscle contraction
Describe what happens during myosin power stroke
Myosin pulling actin, consuming ATP, and resetting
Controlled by calcium
Describe what tropomyosin does
Controls whether actin and myosin interact
Sits on a thin filament in groove of double helix
At rest, TPM covers actin’s binding site for myosin
= Thus, TPM blocks actin-myosin interaction
TPM is pulled out of the way when muscle is active
Describe what the 3 subunits troponin is made up of does (in order)
troponin T : (T = tropomyosin-binding)
troponin C : (C = calcium-binding)
troponin I : (I = inhibitory / binds to actin)
What is the first step in the Cross Bridge Cycle?
Myosin releases actin, binds ATP, releases ADP, resets myosin head angle to 90 degrees
What is the second step in the Cross Bridge Cycle?
Myosin head cleaves ATP into ADP + Pi, which activates myosin head into high energy state that is avid for actin
What is the third step in the Cross Bridge Cycle?
Pi leaves and Myosin head + ADP binds actin, but only if Ca2+ present
What is the fourth step in the Cross Bridge Cycle?
Power stroke: myosin head swivels from 90 degrees to 45 degree angle
What can ACh Receptors vary in? (3 steps)
- pharmacology – what transmitter binds to the receptor and how drugs interact, could be:
agonist - a drug that can combine with a receptor on a cell to produce a physiological reaction
antagonist – a drug that blocks the activity of the agonist or endogenous ligand (neurotransmitter)
- selectivity – what ions are conducted (Na+, Cl-, K+ and/or Ca2+) or none
- conductance – the rate of ionic conduction
What are the ACh Receptor Types? and give exampls of each
Nicotinic receptors
Named after nicotine, an agonist
Example: Neuromuscular junction
2nd messenger is ions flowing (or stopping) through an ion channel — leads to voltage change
Muscarinic Receptors
Named after muscarine (a mushroom toxin), An agonist
Example: parasympathetic nervous system
2nd messenger is G protein
Describe what a nicotinic ACh Receptor does
When activated there is an increase in voltage inside
= Allows both Na+ to flow in and K+ to flow out
-> The Net effect is inward current
More Na+ goes inward than K+ goes outward
= It is called a “non-selective cation channel”
This may trigger an action potential in the post-synaptic cell
Formally: it makes AP firing more likely
Give the name of an example of ACh Receptor (Nicotinic) Agonist
Carbachol (miosis – treating glaucoma)
What do ACh Receptor (Nicotinic) Antagonist do?
Muscle paralysis (relaxes muscle)
Give the name of an example of ACh Receptor (Nicotinic) Antagonist
Rocuronium (tracheal intubation)
Curare (paralysis of diaphragm)
What does an AChE (esterase) inhibitor do?
By blocking breakdown in the cleft longer = which increases ACh activity
Give the name of an example of an AChE (esterase) inhibitor
Donepezil (Aricept) for Alzheimer’s
What is Rigot Mortis?
ostmortem change resulting in the stiffening of the body muscles due to chemical changes in their myofibrils
Describe what happens in rigor mortis
ATP depleted after death
Muscle cell does not resequester Ca2+ into SR = increases Cytosolic Ca2+
Ca2+ allows crossbridge cycle contraction
Until ATP & creatine-P run out
W/o ATP, myosin stops just after power stroke
With myosin still bound to actin
Rigor mortis ends when muscle tissue degrading after 3 days
