Flashcards in Physiology and Pharmacology Deck (70)
Describe the composition of the membrane
Phospholipid bi-layer- stable barrier
What makes up the Extracellular Fluid?
Plasma and interstitial fluid
Name cations in the ECF and ICF
Sodium, Potassium and Calcium
Names anions on the ECF and ICF
Bicarbonate, Chloride, Phosphate, Proteins
State the difference in concentration of Sodium in ECF and ICF
State the difference in concentration of Potassium in ECF and ICF
State the difference in concentration of Calcium in ECF and ICF
State the difference in concentration of Bicarbonate in ECF and ICF
State the difference in concentration of Chloride in ECF and ICF
ECF: High - varies approx. 100mM
This depend on type of cell
State the difference in concentration of Phosphate in ECF and ICF
ECF: Low- 3-4mM
ICF: High, many bound within adenosine in ATP, low conc of free phosphate in fluid
State the difference in concentration of Proteins in ECF and ICF
Roughly same concentration in both ECF and ICF
Slightly higher in ICF - many of cell membrane
In the ECF there are more in the plasma compared to the interstitial fluid
What are the different classifications of membrane proteins?
ion channels, carriers and pumps/ATPases
What is the function pumps/ATPases?
Allow solutes to move in absence of or against electrochemical gradient.
Use ATP directly to move solutes against potential/electrical gradient and concentration gradients
What type of transport do pump/ATPases use?
Active transport- as they use ATP
What is the turnover like in pumps/ATPases? and why?
due to extra processing its much slower
Describe the pump/ATPase mechanism
Hydrolyses ATP to produce ADP and a phosphate
Phosphorylation of the protein by adding phosphate
this causes of conformational change
Give an example of an pump/ATPase
Discuss the structure and function of Na/K ATPase
Ubiquitous, tetramer (2 alpha and two beta subunits)
Maintains low intracellular Na concentration
Sets up driving forces for secondary active proteins
Whats an electrochemical gradient?
when both potential gradient and concentration gradient impacts on whether an ions moves
Why is Na/K ATPase electrogenic?
transports 3 positive ions out and 2 positive ions in
each turnover losing a positive charge
impacting on membrane potential
What is the function of a Carrier?
A specific transport protein for ions and solutes.
Allows ions and solute to move across membrane by facilitated diffusion.
what type of transport is a carrier?
Passive - no energy required
Describe the mechanism of a carrier
Binding of two molecules which bind to a binding site.
Conformational change of protein.
Dissociates due to low concentration gradient.
State an example of an carrier
Sodium Glucose Transport
Describe structure and function of a carrier
Secondary active transport
What is meant by secondary active transport?
Relies on NaKATPase to set up a driving force for Na influx
Describe carrier saturation and what does this mean?
Carriers have a maximum turnover and maximum number of transporters
Its carrier mediated diffusion.
Name the classifications of carriers
Uniporter, symporter (co-transport) and antiporter (exchanger)
Why does blocking Na K ATPase inhibit Na Glucose transport?
Need a concentration gradient of high Na outside cell and low Na inside cell, so Na can bind with Glucose and bring Glucose with it into cell.
NaGlucose transport needs a low intracellular Na conc to function.
What type of transport do channels have?
Passive transport- no energy needed
What is the main property of channels?
They are gated, which allows ions to flow through.
How do Ions move through a channel?
Through the pore, ions move down their electrochemical gradient.
What will ions generate as the move through a channel and why?
Create a current as they are charged - this can be measured
Do channels have a high or low turnover?
High, 10^6 to 10^8 ions per second
What is the selectivity for Ion channels
Na, Cl, K, Ca also non-selective
How can we measure ion channels? and what is it a measure of?
Patch clamp technique, direct measure of function of ion channels
How does the Patch clamp technique work?
- Patch pipette filled with salt solution - seal onto surface of cell
- Silver electrode (chlorided) connected to equipment
- Look at any ions underneath pipette tip
- Measure current moving across the patch with respect to 0.
Whats the difference between cell-attached configuration and whole cell configuration?
Cell-attached configuration is where the patch pipette is attached to cell.
Whole cell configuration is where the patch of membrane under tip is removed.
Describe whole patch cell configuration
- salt solution washes intracellular fluid so the composition is set
- current flow of whole cell is measured
- Total current flow across cell membrane
What is the equation for the total current carried by population channels
(look up and describe)
How can you regulate the channels?
Activate or inhibit other channels
(look further into)
Describe Voltage gated K channels
Subunits made by Kv genes
One subunit has: 6 trans-membrane spanning domains, voltage sensor, pore region
4 subunits come together
Describe Ach receptor
4 transmembrane spanning domains
Describe voltage gated Na channels
24 transmembrane spanning domains
4 blocks of 6
4 voltage sensors
4 pore regions
other beta subunits that regulate
2 transmembrane domains
No voltage sensors
4 subunits come together to make functional
Describe CFTR Cl- channel
12 transmembrane spanning domains
Describe the crystal structure of bacterial K channel
A pore down the middle
More than one ion in the pore at any one time - continuous
Describe a method for measurement of membrane potential
Glass electrode - a small sharp tip sitting in the ICF compartment
Measure potential with respect to reference electrode sitting in bath (ECF)
Filled with solution ie Potassium Chloride
A chlorided silver wire connects electrode to equipment
List the concentrations and relative permeability of Na
High ECF- 150mM
Low ICF- 15mM
Relative permeability- 1
List the concentrations and relative permeability of K
Low ECF- 5mM
High ICF- 150mM
Relative permeability- 50-75
List the concentrations and relative permeability of Anions
Relative permeability- 0
What are the Na and K concentrations maintained by?
Na K ATPase
What is the contribution of Na K ATPase to the membrane potential?
- 20% of resting membrane potential directly
- Each turnover means loss of 1 positive charge leaving a negative charge behind
- Maintains a driving force- so Na and K can also contribute to the membrane potential
What is the contribution of K channels to the membrane potential?
- High concentration in ICF, low concentration in ECF: a concentration gradient
- K leaves the cell through K channel so ICF becomes more negative
- Anions allow a negative membrane potential as cannot cross cell membrane
- Negative membrane potential impacts on movement of K, so there is a driving force for K to move back into cell
How does K reach equilibrium?
- potential gradient and concentration gradient become balanced- no net movement
- so no current is generated but still movement of ions
What is the contribution of Na channels to the membrane potential?
- High ECF, Low ICF: a concentration gradient for Na to move into cell carrying a positive charge with it
- ICF becomes more positive
- This positive ICF starts to repel positive Na creating a potential gradient in the opposite direction
How does Na reach equilibrium?
- concentration gradient and potential gradient will become balanced
- no net movement so no current
- still movement of ions
What does a more negative membrane potential mean?
More K channels open. Nernst potential for K
What does a more positive membrane potential mean?
More Na channels open. Nernst potential for Na
How can we use the Goldman equation?
Gives an idea of what the Vm of the cell should be using relative permeability
Calculate Vm of a cell
Calculate the equilibrium for an ion
(go work out an example)
Use the Goldman equation to calculate theoretical membrane potentials
(go work out an example)
Give examples of electrogenic transporters that alter the membrane potential
Voltage gated Na channels
Na coupled co-transport
Describe how Voltage gated Na channels alter the membrane potential
- Action potentials
- Has Nernst potentials for both Na and K
- K and Na trying to drive membrane potential to their Nernst
- At rest: only K channels open
- Depolarization: Na channels trying to move Vm to their Nernst
- Reaches threshold: voltage gates Na channels open driving Vm to their Nernst
- Repolarisation: Na channels close, K open driving Vm to their Nernst
- Over shoot: Voltage gated K channels close
Describe how Na amino acid co transport alters the membrane potantial
- Phenylalanine goes into cell with Na.
- Na drives Vm more positive to its Nernst
- Causes depolarisation
- K channels activation drives Vm towards Nernst for K
- Causing repolarisation
- For Amino acid co-transport to work, the opening of K channels and depolarising of membrane sets -70mV which is the driving force for co transport.
- Repolarisation maintains the driving force for co-transport
What determine Vm?
Unequal distribution and selective movement of ions (Na, K, Anions)
What do ion channels do to membrane potential?
(look in book and write here)
Describe the simplified Nernst equation
(look in book and write here)
What is the nernst potential?
(look in book and write here)