SESSION 4 Flashcards
What is the Nernst equation?
It gives the equilibrium potential of an ion:
Eion = RT/ZF In [ion] out/[ion]in
R is the Gas constant
T is the absolute temperature
F is faraday’s number
Z is the valency (+1 for K+)
[ion]out is the extracellular concentrations of the ion
[ion] in is the intracellular concentrations of the ion
What is responsible for the unequal distribution of inorganic ions between the intracellular and extracellular fluid?
Selective permeable ion channels
Resting cell membranes are selectively permeable to K+. Given the concentration gradient that exists across the plasma membrane, which direction would you expect K+ ion will move?
What effect will this have on the membrane potential and why?
As a result of the concentration gradient - more potassium inside the cell
You would expect K+ ions to move out of the cell
This will hyperpolarise the membrane as the inside of the cell will become more negative
Extracellular concentration of K+ - 4.5
Intracellular concentration of K+- 160
Using the Nernst equation, calculate the K+ equilibrium potential (Ek) for the cells
61/1 log [4.5/ 160] = -94.6/ -95
The actual membrane potential of a nerve cell, when measured by a micro-electrode, was found to be different to that calculated, why?
Potassium ions are not the only ions moving across the membrane, therefore they affect the value
What contribution does the Na+ K+ ATPase make to the maintenance of the resting membrane potential ?
2 potassium ions in
3 sodium ions out
Pump brings the potassium ions back inside the cell
Essential for maintaining the electrical gradient
Some neurotransmitters act to increase Cl- conductance in the postsynaptic cell. What are the consequences of an increased Cl- conductance for the membrane potential?
Chloride ions move from outside the cell to inside
This increased the negative charge within the cell
Resulting in hyperpolarisation
During the initial phase of action potential in nerve and muscle plasma membranes the Na+ permeability increases.
What will happen to the membrane potential?
More sodium will enter the cell
This results in the cell become more positive
Therefore depolarisation takes place
The membrane potential is restored rapidly to resting levels in nerve and muscle cells after an action potential.
How is this achieved?
Does the same thing happen in non- excitable cells?
Sodium channels close and potassium channels open therefore the charge within the cell will rapidly decrease- repolarisation
In non- excitable cells the same thing would happen
During the heartbeat myocardial Ca2+ channels open and result in a substantial increase in Ca2+ permeability.
In which direction does the Ca2+ flow?
Calcium flows intracellularly
Calcium is released from T-tubules and rapidly increased in the cytoplasm
This calcium is required for initiating the muscle contraction
Results in depolarisation of the cell
What would the clinical consequences be for a hyperkalemic patient with a plasma concentration of 7.5mM
This is an abundant amount of potassium outside the cell
There would therefore be a huge influx of potassium ions
Resulting in depolarisation
Potassium can be toxic in large amounts
This massive influx results in contractions
May even result in arrhythmia in the heart
How can membrane potentials be measured?
Using a microelectrode
Skeletal and cardiac muscle have the largest resting potential
Nerve cells have resting potentials in the range -50- -75mV
What are ion channels characterised by?
Selectivity:
Channel selective for Na+, K+, Ca2+, Cl-
Gating:
The channel can be open or closed by a conformational change in the protein molecule
High rate of ion flow down the electrochemical gradient
Define potassium equilibrium potential (Ek)
The membrane potential at which there is no net movement of K+ ions
It can be calculated using the Nernst equation
Describe how the resting potential is set up
At rest, the membrane has open k+ channels
K+ ions diffuse out of the cell, down the concentration gradient
Since anions cannot follow, the cell becomes negatively changed inside
Results in an electrochemical gradient–> potassium ions want to move both in and out of the cell- no net movement
So the system will come into equilibrium
Describe the relationship between ion permeability and the resting potential
Open k+ channels dominate the resting permeability, so the RP is close to Ek (-95mV)- however the membrane is not perfectly selective
The dependence of the resting potential on K + permeability means that changing Ek will change the RP
Increasing K+ outside makes Ek more positive and so changes the membrane potential in the same direction
E.g. Cardiac (-80mV) and nerve cells (-70mV) –> RP is close to Ek
But not perfectly selective
Erythrocytes (-9mV) –> virtually no selectivity for K+
Skeletal muscle (-90mV) –> close to both Ecl and Ek
Define depolarisation
A decrease in the membrane potential, so that the inside of the cell becomes less negative
Opening of Na+ or Ca2+ channels
Define hyperpolarisation
An increase in the membrane potential, so that the inside of the cell becomes more negative
Opening K+ or Cl- channels
Define repolarisation
An increase in the membrane potential, so that the inside of the cell becomes less positive
What are the three main ways in which channels are gated?
Ligand gating:
The channel is opened by binding of a chemical ligand
E.g. Channels at synapses that respond to a neurotransmitter
Voltage gating:
The channel opens or closes in response to changes in the membrane potential
E.g. Channels involved in action potential
Mechanical gating:
Channels open or close in response to membrane deformation
E.g. Channels in mechanoreceptors; carotid sinus stretch receptors
Explain the difference between the fast synaptic transmission and the slow synaptic transmission
Fast synaptic transmission receptor is a ligand- gated ion channel
Two functions:
- bind its cognate receptor
- act as a ion channel
Slow synaptic transmission receptor is not an ion channel, but signals to the channel in one of two ways, both involving GTP binding protein:
1) direct G- protein gating:
- localised
- quite rapid
- G protein has to move-slow, but as it is localised= rapid
2) gating via an intracellular messenger
- throughout the cell
- amplified by cascade
- activates an enzyme causing a signalling cascade, activated the channel, number of intermediate= slow
Define excitatory postsynaptic potential (EPSP)
Depolarising transmitter open channels
Channels selective for Na+ and Ca2+
Lead to excitation of cells - more likely to fire an action potential
Change in membrane potential is called EPSP
- longer time than action potential
- graded with amount of transmitter
- transmitter include: acetylcholine, glutamate and dopamine
Define inhibitory postsynaptic potential
Hyperpolarise got transmitters Channels selective for K+ and Cl- Lead to inhibition - less likely to generate an action potential Change in membrane potential Transmitters include: glycine and GABA
Define membrane potential
Membrane potential is the magnitude of an electrical charge that exists across a plasma membrane and is always expressed as the potential inside the cell relative to the extracellular solution
Membrane potentials are measured in millivolts
Explain the concept of selective permeability
The phospholipid bilayer:
- hydrophobic interior
- permeable to small uncharged molecules
- very impermeable to charged molecules
Ion channels
- proteins that enable ions to cross cell membranes
- have an aqueous pore through which ions flow by diffusion/ flow in both directions down their concentration gradient
Channel proteins:
- selectivity for one ion species- cation channels
- gating: the pore can open or close by a conformational change in the protein
- rapid ion flow down the electrochemical gradient
Define conductance
The contribution of each ion to the membrane potential will depend on how permeable the membrane is to that ion
Real cell membranes have channels open fro more than 1 type of ion
The GHK equation (Goldman- Hodgkin- Katz) is used to measure the membrane potential
Outline some of the roles of the membrane potential in signalling between cells
Example: the neuromuscular junction, motor neurone terminals release acetyl choline that binds to receptors on the muscle membrane
Nicotinic acetylcholine receptors:
- have an intrinsic ion channel
- opened by binding of acetylcholine (x2)
- channel lets Na+ and K+ through but not anions
- moves the membrane potential towards 0mV - intermediate between Ena and Ek
Describe where synaptic connections occur
Nerve cell - nerve cell
Nerve cell - muscle cell
Nerve cell - gland cell
Sensory cell - nerve cell
Describe two factors that can influence membrane potential
Changes in ion concentration
- most important is extracellular K+ concentration
- can alter membrane excitability, e.g. In the heart so a heart transplant can take place
Electrogenic pumps
- Na+ K+ ATPase- 3 sodium out and 2 potassium in
- makes cell more negative
- responsible for maintaining resting membrane potential
Use the islets of langerhans to explain the clinical relevance of membrane potentials
Islets of langerhans- secretion of insulin
- glucose enter the cell through a channel
- mitochondria metabolise ADP to ATP- increasing the ratio
- ATP attaches to receptor preventing potassium leaving
- the membrane depolarises
- Calcium therefore enters
- the massive influx of calcium stimulates the excretion of insulin through vesicles, via exocytosis
Describe the properties of cardiac ion channels
Selectivity- only permeable to a single type of ion
Voltage- as the cell depolarises or depolarises specific channels open and close
Time dependence- some ion channels are configured to close a fraction of a second after they open
