MnR S4 - Electrical Excitability Flashcards
What factors are action potentials dependant on?
Ion gradients and permeability of membrane
What is the experimental evidence for Na+ being the primary cause of depolarisation?
Peak of action potential changes in manner parallel to changes in ENa
How can voltage clamping be used to investigate mechanisms of action potential generation?
Controls membrane potential at set level so ionic current can be measured
How does patch clamping differ from voltage clamping?
Patch clamping enables current flowing through individual ion channels to be measured
What is the all or nothing principle with regards to generating an action potential generation?
Stimulus must cause depolarisation that reaches the threshold level or an action potential will not be generated
Describe the process of an upstroke of an action potential
- Na+ channels open upon depolarisation to threshold
- Na+ enters the cell
- Membrane depolarises
- More Na+ channels open (positive feedback)
Describe the process of a downstroke of an action potential
- Depolarisation
- Opens K+ channels causing K+ efflux
- Na+ channels become inactivated meaning Na+ influx stops
- Repolarisation
What are the two phases of recovery after an action potential?
Absolute refractory period (ARP) - When nearly all Na+ channels are in the inactivated state
Relative refractory period (RRP) - When Na+ channels are recovering from inactivation, membrane excitability returns to normal as the number of the channels in the activated state decreases
What is accommodation?
Longer lasting stimulus requires larger depolarisation to meet action potential threshold
How does accommodation occur?
- Small number of Na+ channels open during long lasting stimulus and are inactivated
- Less Na+ channels then available to generate action potential
- Smaller action potential peak is reached
- Eventually length of time increases to a point that not enough Na+ channels are available to reach threshold for action potential firing
Describe the structure of voltage gated Na+ channels
- Functional channel made up of one alpha subunit
- One peptide containing 4 homologous repeats
- Each repeat consists of 6 transmemiranous spanning domains
- S4 is made up of positive amino acid residues and is voltage sensitive
How does the structure of K+ channels differ from Na+ channels?
Functional channel consists of 4 alpha sub units
How do local anaesthetics work?
Block Na+ channels and prevent the stimulation of an action potential
Local anesthetic drugs bind more readily to sodium channels in an activated state, thus onset of neuronal blockade is faster in neurons that are rapidly firing. This is referred to as state dependent blockade
Describe the two pathways by which local anaesthetics
Hydrophobic - Not use dependant (pathway always available), lipid soluble so crosses the lipid bilayer and blocks channel. Ionised form cannot pass through.
Hydrophilic - Use dependant (pathway only available when channel open), pronated form of drug can pass through the open channel to block it. The more channels that are open the more are blocked
How can conduction velocity be measured?
Calculated by measuring distance between extracellular stimulating electrode and recording electrode and the time between stimulus and action potential being registered by recording electrode
Outline the relationship between conduction velocity and and fibre diameter
Myelinated nerve fibres - Velocity proportional to diameter
Unmyelinated nerve fibres - Velocity proportional to square root of diameter
What is local current spread?
Change in membrane potential in one part can spread to adjacent parts of the membrane
How can local current spread lead to subsequent action potentials?
Depolarisation in other parts of the axon meets threshold and generates action potential in that location
What is fast conduction velocity (action potential) dependant on?
- High membrane resistance
- Low membrane capacitance
- Large axon diameter
What is the length constant? (membrane conduction)
Distance taken for membrane potential to fall to 37% of its original value
What is capacitance?
The ability to store charge, it is the property of the lipid bilayer
What would be the effects of a high capacitance on local current?
More current to charge the membrane leading to decrease in spread of local current
What is membrane resistance dependant on?
The number of ion channels open
What would be the effects of a low membrane resistance on local current?
More ion channels open causes increased loss of local current which limits spread of local current effect
List the two primary functions of the myelin sheath
- Increase membrane resistance
- Decrease capacitance
How does saltatory conduction occur?
- Reduced capacitance in internodal (the myelin sheath bit, NOT gaps) region due to myelin sheath
- Local current induced by action potential at node of Ranvier spreads further down the axon to next node
- No action firing in the internodal region, only at nodes
- Local current spread is faster than action potential spread over axonal membrane surface causing an increase in conduction velocity
What are the three possible consequences of demyelination of axons?
- Decreased conduction velocity
- Complete action potential block
- Only some action potentials transmitted
