APs Flashcards
Changes in membrane potential from RMP that generate electrical signals (APs, synaptic potentials, receptor potentials) are caused by what?
Changes in the membranes relative permeability to ions.
*The AP is generated by …
The flow of ions through voltage-gated channels.
Increases in Na+ conductance during depolarisation cause Na+ influx to exceed … , creating a net influx of positive charge that causes …
K+ efflux, creating a net influx of positive charge that causes further depolarisation.
What is the increase in Na+ conductance? What does it do?
A regenerative positive feedback cycle. Drives membrane potential towards Na+ equilibrium potential of +55mV.
What piece of clinical evidence demonstrates the role of v-g Na+ channels in AP generation?
Congenital pain sensitivity is caused by mutations in the SCN9A gene which encodes the v-g sodium channel NaV1.7.
What experimental studies demonstrate the role of Na+ conductance in AP generation?
Voltage clamp, Hodgkin and Huxley.
How did voltage clamp method show role of Na+ in AP generation?
Stepping the membrane potential from rest (-60 mV) to a depolarised level (0 mV) reveals a transient inward current, followed by a sustained outward current. Removing Na+ from the extracellular fluid eliminates the transient inward current.
How does the voltage clamp work?
Permits “clamping” of membrane potential at predetermined level. Prevents changes in membrane current from influencing membrane potential. Control of membrane potential allows one to measure the effect of changes in membrane potential on the membrane conductance of individual ion species.
Who did the patch clamp method?
Erwin Neher and Bert Sakmann.
What did the patch clamp method find?
No change in ionic current through v-g isolated sodium channel at -75mV but yes at -55mV.
Why does AP peak never reach +55mV? 2 factors.
Because K+ leak conductance remains, continual efflux.
Also slight influx of Cl- counteracts depolarisation.
What is membrane potential during AP determined by?
The relative permeabilities to different ions, approaching the steady-state membrane potential predicted by the GHK equation.
Why does afterhyperpolarisation occur?
V-g K+ channels no inactivation mechanism.
What does v-g K+ channel closure rely on?
The gradual reversal of the v-g conformational change that opened the channel during depolarisation.
What explains absolute refractory period?
Na+ conductance inactivated, so fraction available for activation insufficient to overcome K+ conductance.
What is the role of the refractory period?
Ensures APs propagate unidirectionally.
What is membrane resistance? What does it do to the rate of change of membrane potential?
How well the cell membrane resists the flow of electrical current. Reflects the permeability of the membrane to ions. Increases rate.
Why does high membrane resistance increase propagation speed?
Less ion channels open at rest, reducing leakage of charge. More depolarising current flows along the axon rather than dissipating across the membrane.
What is membrane capacitance? How is the membrane endowed with it?
The ability to store electric charge. Hydrophillic heads and hydrophobic tails of phospholipids give it an insulating property.
Why does high membrane capacitance decrease propagation velocity?
More charge must be deposited, current requires more time to produce depolarisation.
Why does large diameter increase propagation velocity?
Number of charge carriers per unit length of axon greater. More current enters, depolarised more efficiently. Lower axial resistance.
What is Ohm’s Law? What does it mean for why low axial resistance increases CV?
I = V/R. Less current needed to charge up adjacent membrane segments.
What does axial resistance decrease in proportion to? What does membrane resistance decrease in proportion to?
The square of the diameter. The diameter.
What is the length constant equation? What does it determine? Why is that good for CV?
Squrt(Rm/Ri). How far the current can spread before decaying. Reduces the need for frequent regeneration of AP.
What is the time constant equation? INVERSELY PROPORTIONAL.
Rm x Cm.
Using length constant equation shows the conduction velocity will increase according to …
The square root of the diameter.
What adaptations have evolved to increase CV?
Increase in axon diameter (giant axon of squid, 1mm), myelination.
Why no larger axon diameter than 1mm in giant squid axon?
Need to fit many cells in a small space.
Why does myelination increase CV?
Capacitance inverse to thickness of insulation. Thus decreases T. Also decreases membrane resistance, increasing lambda.
Why salutatory conduction required?
Myelin not a perfect insulator.
Why salutatory conduction metabolically favourable?
Ions flow only at nodes. Less energy needed by Na+/K+ pumps to regenerate conc. gradients.
What is a clinical example of myelination benefits/fast conduction benefits?
MS. Immune attacks on sheaths, slowed conduction. Leads to weakness/paralysis.
What do all three relevant conductances (what are they) do?
Clamo the membrane potential at their Nernst potential.
But the actual membrane potential is determined by the relative permeabilities of different ions, approaching the steady-state membrane potential predicted by the GHK equation.
What confirms that propagation relies on the passive spread of local currents through the axoplasm and across the membrane?
Axial clamp, intracellular electrodes inserted into long axon, precise current injected to manipulate membrane potential, miming current flow that occurs during AP.
Depolarisation in one region of membrane induces a current that depolarises neighbouring regions, thereby triggering an AP in the next segment.
What pharmacological blocker blocks V-g K+ conductance?
Tetraethylammonium ions (TEA+).
What does the patch clamp method provide evidence for?
Effect of changes to membrane permeability of ions in the generation of APs.
Where may myelination be unnecessary?
Autonomic projectons, local projections.
