M&R Session 3 and 4 Flashcards
How is membrane potential measured?
Potassium chloride filled microelectrode penetrates cell membrane conducting its potential
What is the basis of signalling in many types of cell?
Electrical potential difference across the plasma membrane
How is resting membrane potential expressed?
Potential inside relative to potential of solution outside
In mV
What is the range of resting potential in animal cells?
-20 to -90 mV
What is the resting potential of cardiac muscle?
-80 mV
What is the resting potential of skeletal muscle?
-90 mV
What range does the resting potential of nerve cells lie within?
-50 to -75 mV
What is the approximate resting potential of smooth muscle?
-50 mV
What are ion channels?
Proteins with an aqueous pore which enables ions to cross cell membranes
Give three properties of ion channels.
Selectivity for 1/a few ions
Gating by conformational change
Rapid ion flow always down electrochemical gradient
What dominates the membrane ionic permeability for most cells at rest?
Open voltage-insensitive potassium channels
What must be equal and opposite for no net movement of ions across a cell membrane?
Electrical gradient
Chemical gradient
In a resting cell, are the anion channels open or closed?
Closed
Permeability to which ions establishes the membrane potential?
Potassium
What assumptions are made when using the Nernst equation?
Membrane perfectly selective for the ion
Temperature is 37 degrees Celsius
Pressure is standard
What is ‘z’ in the Nernst equation?
Valency (charge)
Describe the behaviour of sodium and calcium channels in the resting cell membrane.
Closed but not perfectly - allow enough ions in to depolarise to -70 mV
What makes skeletal muscle cells have a more negative resting potential?
Chloride channels
Which ion equilibrium potential are cardiac and nerve cells close to?
Potassium
What causes cells to have a higher resting potential?
Lower selectivity for potassium
Increased contribution from other ion channels
Which two equilibrium potentials are skeletal muscle cells close to?
Chloride
Potassium
What is changing membrane potential used for?
Action potentials in nerve and muscle cells
Triggering of muscle contraction
Postsynaptic actions of fast synoptic transmitters
Control of neurotransmitter and hormone secretion
Transduction of sensory input to electrical activity
Define depolarisation.
Decrease in size of membrane potential from normal value
Cell interior becomes less negative
Define hyperpolarisation.
Increase in size of membrane potential from normal value
Cell interior becomes more negative
What changes equilibrium potential?
Altering membrane permeability to a particular ion
In which direction does the membrane potential move when it’s permeability to a particular ion changes?
Towards the equilibrium potential for that ion
Opening of which ion channels causes hyperpolarisation?
Potassium
Chloride
Opening of which ion channels causes depolarisation?
Sodium
Calcium
Which equation is used to consider the relative permeability of several ions within a membrane?
Goldman-Hodgkins
Which ion permeabilities does the Goldman-Hodgkin equation take into account?
Potassium
Sodium
Chloride
How do nicotinic receptors at the NMJ affect membrane potentials?
Drive it towards the average equilibrium for the ions involved
Describe the action of nicotinic ACh receptors.
Have intrinsic ion channels opened by binding of 2 ACh
Channel allows sodium and potassium through but no anions
Moves membrane potential towards the intermediate b/w sodium and potassium equilibrium potentials - 0 mV
How can channel activity be controlled?
Ligand gating
Voltage gating
Mechanical gating
Where are ligand-gated ion channels found?
At synapses that respond to extracellular transmitters
Cells that respond to intracellular messengers
Where are voltage-gated ion channels found?
In cells utilising action potentials
Where are mechanical-gated cells found?
Cells in mechanoreceptors - e.g. Carotid sinus, hair cells, stretch receptors
How do mechanical-gated ion channels work?
Membrane deformation causes the channels to open or close
How is fast synaptic transmission carried out?
The receptor protein is also an ion channel which open upon transmitter binding
Give an example of a fast synaptic transmission receptor.
Nicotinic ACh
How do excitatory synapses work?
Ligand-gated channels are opened –> membrane depolarises as cations move in –> excitatory post-synaptic potential (EPSP) generated
What is different about and action potential and an EPSP?
EPSP has a longer time course
EPSP can be graded by the amount of transmitter which binds
Give two examples of transmitters which can be used at excitatory synapses.
ACh
Glutamate
How do inhibitory synapses work?
Open ligand-gated channels –> hyperpolarisation –> inhibitory post synaptic potential (IPSP) generated
How does an IPSP compare to an AP?
IPSP has a longer time course than an AP
IPSP uses glycine (in spinal cord) and GABA
How does slow synaptic transmission occur?
Direct G-protein gating
Gating via an intracellular messenger
What is a G-protein?
A 7-domain transmembrane receptor
Describe two properties of G-protein gating.
Localised Quite rapid (not as fast as fast synaptic)
Describe the method of gating via an intracellular messenger.
Occurs throughout cell
Amplification by cascade produces new intracellular chemicals
G-protein receptor –> enzyme –> intracellular messenger/protein kinase –> channel
Why is hyperkalaemia very dangerous?
Cardiac myocyte membranes become easily excited –>contraction more easily stimulated
What is the function of Na/K-ATPase in the resting membrane potential?
Contributes a few mV directly by movement of one +ve charge out per cycle
May modify activity
Indirectly accountable for whole membrane potential due to it establishing ion gradients
What must happen for the voltage across a cell membrane to rapidly change?
Threshold level must be reached
What is the term given to the response of a cell dependent on whether the threshold level is reached?
All or nothing
How does the amplitude vary as it travels along an axon?
It remains constant
What causes the repolarisation profile of skeletal muscle to vary in comparison to that of other cells?
Different ion channels
T-tubules
Describe the action potential in a cardiac ventricle cell.
-90 to +30 mV
Over 100 Ms
Describe the action potential in a sino-atrial node cell.
-60 to +30 mV
Over 100 Ms
Describe the action potential in a skeletal muscle cell.
-90 to +40 mV
Over 0.5 Ms
Describe the action potential in an axon.
-70 to + 30 mV
Over 0.5 Ms
Why does opening chloride channels in an axon have minimal effect?
The membrane potential is -70 mV and its equilibrium potential is -96 mV
Which is the most variable equilibrium in muscle cells?
Chloride
Why is the lipid bilayer referred to as a good capacitor?
Can store a lot of charge
Separates two good conductors
What is the effect of reducing extracellular sodium on the action potential?
It reduces the overshoot in membrane potential to the point where it no longer becomes -ve
What changes in parallel to the change in sodium equilibrium?
The peak of the action potential
What is thought to cause the upstroke in an action potential?
A large increase in sodium permeability
What magnitude of movement of sodium ions is required to generate an action potential in an axon of 1 micrometer diameter?
> 0.4%
What different methods can be used to investigate axon potential generation?
Voltage clamping
Change ionic concentrations
Patch clamping
What is the axon hillock?
An area with a high density of sodium channels
What takes place at the axon hillock?
Depolarisation to threshold value activates an axon potential here
What causes the sodium conductance during an action potential to quickly fall away?
Sodium channel inactivation
What causes the delay in potassium channel closure during an action potential?
The potassium conductance
What happens during upstroke of the action potential?
Sodium channels open –> sodium influx –> depolarisation –> to threshold = entry to feedback loop
How is the rate of sodium channel opening increased?
Greater membrane depolarisation
What is the basis of the all or nothing response?
Whether the cell enters positive feedback
Why does the cell not respond if the threshold value is not met?
Too few sodium channels are open
What happens during the downstroke of the action potential?
Depolarisation causes inactivation of sodium channels and after a short delay opens potassium channels –> sodium influx stopped and potassium efflux takes place –> repolarisation
What is the absolute refractory period?
No action potential generated no matter how much you stimulate it
What is the relative refractory period?
Sodium channels recover from inactivation to restore membrane excitability
Compare the duration of the absolute refractory period and the relative refractory period.
ARP = fixed duration - first millisecond RRP = variable duration
What causes a shorter RRP?
More hyperpolarisation (–> faster recovery)
Can sodium channels open from an inactivated state?
No
How are sodium channels recovered from inactivation?
They must be hyperpolarised to become closed and then depolarise to be opened
Can sodium channels be inactivated before the threshold potential is reached?
Yes
What is accommodation in relation to cell membranes?
How the membrane potential determines how excitable the membrane is
What is the affect on a cell membrane of a longer stimulus?
Increased time taken to reach membrane potential
More inactivated sodium channels
Lowered action potential peak
What happens to the threshold potential as the time taken to reach it increases?
It becomes more positive
Does the action potential reach the threshold if it’s peak is lowered by a long stimulus?
No
Will a membrane which is accommodated fire an action potential if the original threshold is surpassed?
No
Where are the ~10,000 continually firing synapses in an axon integrated?
At the dendritic tree
What is the basic structure of a sodium channel?
Repeats I-IV of 6 membrane spanning domains
Functional channel = 1 alpha-subunit
What is the voltage sensor of a sodium channel?
S4 region with lots of +ve residues
Where is the pore region in a sodium channel?
Domains 5-6
What happens to a sodium channel when it becomes inactivated?
Inactivation particle binds 6-1 –> conformational change –> pore blocked
What happens to an inactivated sodium channel to recover it?
Membrane polarised –> change in voltage force –> conformational change –> inactivation particle released
Describe the structure of a potassium channel.
Single 6 membrane-spanning domains unit
Functional channel = 4 alpha-subunits
Similar to sodium channel, just a quarter of the size
What prevents passage of sodium ions through potassium channels?
Its amino acid sequence means the smaller ions cannot pass through easily
What is the action of local anaesthetics?
Block sodium channels
Which two pathways can local anaesthetics take?
Hydrophobic (no use-dependent)
Hydrophilic (use-dependent)
What determines which pathway a local anaesthetic takes?
It’s lipid solubility
Describe the mechanism of the hydrophobic pathway.
Pass through lipid membrane –> block sodium channel pore –> as more action potentials fire more channels are opened –> more channels are blocked –> pain becomes duller
In which activation state of sodium channels do lipid soluble local anaesthetics have greatest affinity for?
Inactivated
When is binding of local anaesthetics in the hydrophobic pathway easiest?
When sodium channels are open
Describe the mechanism of the hydrophilic pathway.
Local anaesthetic becomes charged by combination w/ proton –> binds to and blocks open sodium channel
What must happen for a use-dependent local anaesthetic to work?
The sodium channels must be opened initially
In what order do local anaesthetics block axons?
Small myelinated
Un-myelinated
Large myelinated
Is initial pain experienced in the use of local anaesthetics?
Yes, sodium channels are opened so some initial action potentials are fired
Give two examples of disease states which affect conduction of action potentials in the CNS.
Multiple sclerosis
Devic’s disease
Give two examples of diseases which affect conduction of action potentials in the PNS.
Landry-Guillan-Barre syndrome
Charcot-Marie-Tooth disease
Which nerves does Devic’s disease affect?
Optic
Spinal cord
What are the four classes of peripheral axons?
A-alpha
A-delta
B
C
What are A-alpha peripheral axons?
Sensory fibres from muscle spindles
Motor neurones to skeletal muscle
What are A-delta peripheral axons?
Sensory fibres from pain and temperature receptors
What type of pain do A-delta peripheral axons give rise to?
Sharp, localised pain
What are B peripheral axons?
Preganglionic neurones of the ANS
What are C peripheral axons?
Sensory fibres from pain, temperature and itch receptors
What kind of pain do C peripheral axons give rise to?
Diffuse pain
What is diphasic recording?
Stimulating and recoding electrodes are placed on the axon during extracellular recording of an action potential
What is monophonic recording?
A portion of axon is deliberately damaged underneath/before the recording electrode to stop the action potential
What is a nerve fibre made up of?
Several axons w/ different diameters
How is the action potential of a nerve fibre described?
Compound
What does increasing the distance from the stimulus that the action potential is measured do?
Gives greater action potential peak separation (monophasic recording)
What is the length constant (lambda)?
The distance taken for the action potential to fall by 37% (1/e) of its original value
What does the length constant depend on?
How far along the axon the action potential travels
Describe the mechanism of the local current theory
Sodium in –> repels +ve ions w/in axon –> ions spread in either direction –> immediate local current
Does the immediate local current depolarise as much as the original stimulus?
Nope
What affect does an increase in capacitance have on a axon’s electrical properties?
Increases time taken to reach a steady voltage
Does not directly affect length constant
What decreases length constant at the action potential downstroke?
Open potassium channels
What prevents right to left transmission of nerve impulses?
Inactivation of sodium channels
At what diameters is it not worth having myelination?
< 1 micrometer
What holds the myelin sheath tightly in place around axons?
Proteins
Describe the function of Schwann cells in myelination.
Myelinate PNS axons
Myelinate one axon each by pushing previous layers further from the centre
Describe the role of oligodendrocytes in myelination.
Myelinate CNS axons
Myelinate up to 50 axons each
How does myelination increase the speed of action potential transmission?
Saltatory conduction
How does myelination affect the electrical properties of an axon?
~100x increase in membrane resistance
~100x decrease in membrane capacitance
Therefore…
Increase length constant and decrease time constant
What is found at a Node of Ranvier?
Increased densities of ion channels
How does saltatory conduction work?
Local circuit current depolarises the next node of Ranvier above threshold –> initiates an action potential
What is the relationship b/w conduction velocity and diameter of axon in unmyelinated axons?
Velocity is proportional to the square root of diameter
How is local current spread altered in saltatory conduction?
It is greatly increased
How does demyelination alter the electrical properties of an axon membrane?
Decreases its resistance and increases its capacitance
What is the result of demyelination of an axon?
The action potential at the subsequent node is not above threshold –> no conducted
Briefly describe the process of Multiple Sclerosis.
Multiple areas of CNS damage –> areas determine symptoms –> eventually leads to axon damage
What magnitude is the ion movement during the generation of an action potential?
Small - relatively few ions move
Is Na/K-ATPase used for action potential repolarisation?
No
