Lecture 3: Voltage-Dependent Membrane Permeability Flashcards
Describe the voltage clamp method
- one internal electrode (connected to the voltage clamp amplifier) measures membrane potential
- the voltage clamp amplifier compares membrane potential with the desired (command) potential
- when the membrane potential is different from the desired potential, the clamp amplifier injects current through a second electrode, this feedback arrangement causes the membrane potential to become the same as the command potential
- the current flowing back into the axon and thus across its membrane can be measured, permitting the measurement of the exact current needed to keep the cell at a given voltage
What happens when membrane potential and command potential are the same?
The feedback causes the membrane potential to remain constant
What happens to membrane current when you apply and hold a hyperpolarizing current?
get a capacitive current, caused by redistribution of charge across the neuronal membrane and occurs briefly but holding the current doesn’t do anything to the membrane current
What happens to membrane current when you apply and hold a depolarizing current?
get a capacitive current then a transient inward current that goes back to 0 and if you hold the current, get a delayed outward current after a few seconds
What is axon membrane permeability dependent on?
voltage
What happens to membrane current at several different depolarization potentials?
from negative, zero, and increasingly positive mV: small transient inward curve and delayed outward curve, then larger transient inward curve and delayed outward curve, then smaller transient inward curve but a larger delayed outward curve, then transient inward curve lost but a larger delayed outward curve and then transient inward curve slightly outward and larger delayed outward curve
What ion is responsible for the transient inward curve?
sodium
What happened when sodium was removed from the extracellular saline solution?
The early inward curve is gone, now a small early outward current and a big outward curve
Describe the pharmacological separation of sodium and potassium currents into sodium and potassium components
When they added tetrodotoxin, it blocked Na+ channels, and the transient inward curve was gone but the delayed outward curve was there
When they added tetraethylammonium (TEA), blocked K+ channels and when they held the MP to 0, still got transient inward current but the delayed outward current was gone so the delayed outward current is dependent on potassium
What did the experiments regarding the membrane changing to a more positive level than resting potential produce?
An early influx of Na+ into the neuron produces a transient inward current.
A delayed efflux of K+ produces a sustained outward current.
In general, what effect does depolarization have on sodium and potassium conductance?
Increases
What does depolarization of the neuronal membrane result in?
(1) Na+ conductance activation
(2) K+ conductance activation
(3) Na+ conductance inactivation
true or false: sodium and potassium conductances change over time
true
true or false: sodium and potassium conductances are voltage-dependent
true
What happens if you stimulate the membrane potential at a time close to the first action potential?
nothing happens because of the refractory period (Na+ channels are inactivated) but if you wait a bit longer, you can generate an AP but now you’re stimulating a membrane that’s been hyperpolarized, resulting in a smaller amplitude AP
What feedback cycles are responsible for membrane potential changes during an action potential?
the fast positive cycle and slow negative cycle
What happens in the fast positive and slow negative cycles?
when you depolarize this leads to Na+ channels opening, leading to an increase in Na+ current which further depolarizes the current but eventually Na+ channels become inactive and while this happens, it has a slower effect that opens K+ channels and this hyperpolarizes the membrane potential
true or false: action potential conduction doesn’t require both active and passive current flow
false, it requires both
Explain the steps of action potential conduction
- A certain point on the axon is stimulated, resulting in an action potential due to local sodium channels opening
- passive current flow moves down the axon and decays but it can lead to local depolarization at a new point on the axon which causes sodium channels to open at this new point and generates an action potential
- upstream sodium channels get inactivated while some potassium channels open and now the membrane is repolarizing at the previous point and it’s in the refractory period
- this process repeats continuously, due to a delay as passive current is activating point B after point A and activating point C after point B
What is the role of the refractory period?
Limits the number of APs that a neuron can produce per unit time
Prevents re-excitation of the same membrane segment that was just excited
Prevents APs from propagating backward toward their point of initiation
What is conduction velocity?
how long it takes for an AP to propagate from one end of a neuron to the other
What are the 2 ways to increase conduction velocity or passive flow?
Increase the axon diameter
Myelinate, which leads to saltatory conduction in which generation of the AP occurs only at the Nodes of Ranvier, which is the only place along the axon where voltage-gated Na+ channels are found
Where are sodium channels found in myelinated neurons?
Nodes of Ranvier
true or false: Nodes of Ranvier are myelinated
false
What is the advantage of myelination?
Allows passive flow of current further down the axon, faster vs. an unmyelinated axon
What is multiple sclerosis?
a disease of the central nervous system that is characterized by a variety of clinical problems that arise from demyelination and inflammation of axonal pathways
What is thought to be the cause of multiple sclerosis?
the immune system produces antibodies against myelin proteins, leading to demyelination, and disrupts an axon’s ability to conduct APs, which is why you see a variety of clinical problems
