Membrane Permeabilties And Action Potentials Flashcards
What type of molecules can diffuse through membranes?
Small, uncharged polar molecules (H20, urea) Hydrophobic molecules (O2, N2) Large uncharged but polar molecules can but very slowly
What is the permeability coefficient?
A measure of how quickly a substance will pass through a semi permeable membrane
What two factors does rate of passive transport depend on? is this fixed or will it change if you change other factors?
The concentration gradients and the permeability coefficient.
It will change, depending on specific membrane, specific substance and at differnt points over time- eg after depolarisation
What are the 3 models for facilitated diffusion proteins action?
Flip flop- carrier protein flips when ligand binds so it faces the inside of the membrane. However this uses lots of energy and only really seen during apoptosis
Ping Pong- When ligand binds conformational change exposes inner membrane and blocks extracellular space, only transports 1/2 molecules at a time though
Channels- Stimulus (voltage change, ligands (ach), ATP…) causes channels to open to allow ions to freely pass through to inside of cell
Is ∆G (gibbs free energy change) for active transport positive or negative?
Positive- as transport up a conc gradient is not thermodynamically favourable and requires energy
When calculating ∆G what can log10 be substituted for?
8.314
What is the difference between primary and secondary active transporters?
Primary uses energy directly from ATP to move substances up a conc gradient
Secondary uses conc gradients already set up by primary active transporters to move substances up a conc gradient
What are the two types of transport?
Uniport- one type of molecule at a time (PMCA only moves Ca2+)
Cotransport- moving two or more molecules at a time
What are the two types of cotransport? Give examples
Symport- moving two types of molecules at the same time in the same direction (Glucose and Na+ in gut epethilia)
Antiport- moving two types of molecules at the same time but in different directions (Na/K ATPase moves 2 Na out and 3 K in)
What is the concentration of Ca outside and inside the cell?
Out= 1mM In= 100nM
Is the concentrations of K, Na and Cl higher or lower outside the cell?
K+= lower outside the cell Na+= higher outside the cell Cl-= higher outside the cell
Describe the structure of the Na/K ATPase pump (P type)
The alpha subunit contains K, Na and ouabain (an inhibitor) binding sites. It crosses cell membrane. On the inside of the membrane there is an aspartate which ATP phosphorylates to create the conformational change to allow Na and K to move. There is a beta subunit which contains a glycoproteins which directs it to the cells surface
Why is the SERCA not a pump? What is it?
Because pumps are only found on the external plasma membrane of a cell. It is an ion transporter
What happens to the NCX in ischemia?
Inadequate blood supply to tissue means less ATP available. Therefor Na/K ATPase cannot function. Na therefor accumulates in the cell. This causes the NCX to reverse (3 Na out 1 Ca in), high Ca inside the cell is toxic to the cells.
How is pH of a cell in increased?
The NHE pushes one H+ out and one Na+ in, to increase the pH in the cell when it is too low. The NBC (sodium dependant chloride/ bicarbonate exchanger) uses Na moving in to move H+ out, Cl- out and HCO3- in (notice all charges balance so no electrical potential effect)
What pump is used to decrease pH of a cell?
The Cl-/ HCO3- anion exchanger (AE) removes Bicarbonate from the cell and bring one Cl- in down its concentration gradient.
How many water molecules move with K+, Na+ or Cl- when they move in/out the cell?
6
Name 3 transporters which remove water/ ions overall so resist cell swelling?
Cl- uniport active transporter move it out cell
K+ uniport facilitated diffusion moves it out cell
K+/ Cl- cotranpsorter moves both out cell at same time
Amino acids moved out
What activates and inhibits the NHE?
Activated by growth factors
inhibited by amiloride
name 3 mechanisms that resist cell shrinking?
NCX- 3 Na in and only 1 Ca out so overall inward movement of ions so overall inward movement of water
Na/ Cl symporter moves both Na and Cl- in down their conc gradient
Na and glucose both transported in together
Na/ Cl pump both with K coming in up its conc gradient with Na coming in down it.
How is glucose transported into the cells of the kidney and intestinal epithilium?
Na/ K ATPase moves Na out epithelial cell. Na+ conc in cell therefor lower than in lumen, Na/ Glucose symporter brings glucose in up conc gradient and Na in down conc gradient. GLUT2 transporter takes glucose out.
How is glucose transported into skeletal muscle, adipose tissue, liver and brain?
Insulin dependant- insulin must first bind to insulin receptor on cell membrane.
This activates a cascade
Which causes GLUT4 vesicle to fuse w/ plasma membrane
Glucose can therefor diffuse through GLUT4 uniporter
As it enter the brain it is phosphorylated to glucose-6- phosphate to maintain a concentration gradient. It is then converted into glycogen/ fats ect. This stops glucose leaving the cell when blood glucose levels drop.
Do all cells have negative resting potential?
yes but some larger than others
Erythrocyte= -9mv
Skeletal muscle= -95mV
How can the resting membrane potential be measured?
Microelectrode glass pipette is made by stretching heated glass to give it a tiny end
Glass pipette is filled with KCl to conduct charge and glass pipette penetrates cell membrane
Another electrode is placed outside cell in extracellular solution. voltmeter and wires passed between the two electrodes and voltmeter will detect the potential difference.
How is the resting membrane potential set up?
Na and K conc gradients set up by Na/K ATPase
K+ selective channels are open meaning K+ can leave down con gradient
However Na+ cannot enter down congradient as Na+ selective channels are closed. Ca cannot enter either.
K+ leaving means more + on outside than inside to inside the cell becomes more negative.
However as this happens some K+ wants to enter as it is attracted to the - charge. An equilibrium is established between K+ leaving down conc gradient and K+ coming in down electrical gradient. This is the equilibrium potential of K+.
The interaction of the equilibrium potential of all ions creates the membrane potential, but since K+ is the main mover, its usually pretty close to K+s- -95mv
What is the equilibrium potential (Ek) of an ion?
The potential difference across a membrane needed to cause no net movement of ions as there is balance between electrical and chemical gradients.
What equation can be used to calculate equilibrium potential? What does the equilibrium potential depend on?
Nerst equation.
Conc gradient between ions
Valency (charge) of ions
What ions would a cell have to be permeable to, to make its membrane potential less negative (more positive- depolarisation)?
Na and Ca- as they would move in down their conc gradients.
What ions would a membrane have to me more permeable to to make the cell more negative (hyperpolarisation)?
Cl- as it would move in down its conc gradient.
K+ as it would move out.
What is the name for how permeable a membrane is to a particular ion? What equation can be used to combine membrane permeabilities and find to overall voltage of a cell?
Conductance
GHK equation
Other than ion channel activity, what influences membrane potential?
- changes in ion concentrations- higher extracellular [k+] means higher equilibrium, and so membrane potential meaning the cell will be more easily depolarised to threshold
- Na/ K ATPase pump- contributes a few mV to membrane potential, but also establishes conc gradients.
How is insulin secretion triggered by membrane potential changing?
high ATP from high glucose levels cause K+ channels to close in pancreas so cells depolarise and cause Ca to move in which triggers insulin vesicle release.
How does an action potential propagate and spread?
- Stimulus causes sodium influx
- If depolarisation meets the VONCs threshold (volatage operated/gated Na+ channel), VONC open and VOOKC open (K+ channel)
- VONC open much faster, rapid influx of Na causes membrane depolarises to +40mv
- As soon as VONC opens it is deactivated by particle, so Na+ influx stops
- Now VOKC are opening, K+ is leaving and repolarising cell
- Too much k+ leaves, causing hyperpolarisation.
- VONC reactivated by hyperpolarisation but they closed
- The few excess K+ ions are moved back by Na/K ATPase pump and maintained by selective permeability.
Why is there only a consequence if the Na/K ATPase pump doesnt work for 100s of action potentials?
Because only very few ions move meaning it plays a minor role in establishment. However over 100s of action potentials lots of ions have moved and the pump is needed to correct the concentrations.
Describe the structure of the voltage operated sodium channel.
- a single polypeptide
- w/ 4 major domains
- each major domain has 6 trans membrane domains
- H5 TRM is poreforming region
- 4th TRM is + charged amino acids which will move on depolarisation to cause conformational change of channel
- N and C termi on inside of cell
- inactivation particle moves into pore on opening to inactivate it
What’re the differences between the voltage tagged sodium channel and the voltage gated pottasium channel?
Pottasium channel has 4 differnt polypeptides.
It is selective to K not Na
No inactivation particle.
What is the absolute (ARP)and relative refractory periods (RRP)?
ARP- the rise and fall on the graph- new action potential cannot be generated no matter how strong the signal as Na+ channels either open or inactivated
RRP- periods of hyperpolarisation and rise again back to resting potential- Na channels are starting to be reactivated (but closed), a action potential could be propagated if stimulus strong enough to depolarise to threshold.
How do local anaesthetics work? Give an example of one
They move into the voltage gated sodium channels pore then open and block them and then they stay there when the channel is inactivated to keep on blocking the channel. This means you cannot depolarise fully even after hyperpolarisation even if you meet threshold because even the the pore may open it is blocked so Na will not enter the exon.
Procaine/ Lidocaine.
Give the order that local anaesthetics block axons in.
Small myelinated
Unmyleinated
Large myelinated
Describe how the local current theory works
When Na+ enter the axon they repel (as all positivly charged), and so depolarise the regions around it. The amount of depolarisation will decrease the further away from the action potential you get because resistance in the cytoplasm will stop Na moving, and also Na ions move out and Cl/ K ions move in to balance the charge. In unmyelinated axons the depolarisation down stream of the axon causes the next voltage gated sodium channel to open and so the action potential spreads downwards. It cannot go backwards as sodium channels up the axon are inactivated (ARP)
How does myelination increase speed of action potential?
- Decreases rate of spacial decay of a the potential (gamma) by: Increasing resistance between nodes (less ion channels) and also increasing distance between + and - charges, both of which result in lower capacitance
- Therefor depolarisation spreads further and so reaches threshold further away (at node of ranvier) and this leads to action potential jumping from node to node (saltatory conduction)
What % of the width of a myleinated axon is axon diameter and what % is myelin sheath?
70%= axon 30%= myelin
How does myelin sheath form?
swchann cell comes into contact with axon and then wraps/ spins around it many times and the cytoplasm is forced out and then it is left with many layers of phospholipid bilayer (Myelin)
