Lecture 7: Resting Membrane and Action Potentials Flashcards
Why do cells become excited and what are excitable tissue?
Cells become excited so that they are able to communicate with their interior or other cells.
Nerves and muscle.
How do cells become excited?
Prior to cells becoming excited, they begin at their resting membrane potential. In order for them to become excited, a signal is needed to activate and transmit it.
RMP changes from rest based on
Changes in charge across the membrane due to
- Different ions
- Different electrochemical gradients
Muscles rely on changes in resting membrane potential to do what?
They rely on signals received from motor neurons to initiate contraction in a process called excitation- contraction coupling.
Are all signals the same?
No. Some are graded potentials and some are action potentials.
Skeletal muscle concentrations of K+
Inside: 155mM
Outside: 4.5mM
Skeletal muscle concentrations of Na+
Inside: 12mM
Outside: 145mM
Skeletal muscle equilibrium potential for K+
-95mV
Skeletal muscle equilibrium potential for Na+
+67mV
In skeletal muscle, which has a higher concentration inside the cell: K or Na+.
K+ (155 inside/4.5 outside)
Na+ has a higher concentration outside (145 outside/12 inside)
How do we get a RMP?
K+ is higher inside the cell and Na+ is higher outside, resulting in a RMP that is (-).
This is due to the K+ leak channels and the Na/K ATPases.
K+ will flow out of the cell via K+ leak channels and be brought back in through Na+/K+ ATPases, which will move 3 Na+ out while bringing 2 K+ in.
RMP is primarily due to the permeability of the plasma membrane to ____________ ions.
K+
Is the membrane permeable to K+, Ca2+ or Na+
The membrane is somewhat permeable to K+, but not to Na+ or Ca2+.
Movement across the membrane to establish the RMP is controlled by what?
- K+ leak channels
2. Na/K ATPases.
Na+/K+ ATPases move how many Na and K?
3 Na+ out
2 K+ in
K+ leak channels
K+ leak channels are open all of the time and permit the unregulated passage of cells.
They are present at a 100:1 ratio compared to Na+ leak channels.
Is K+ more likely to leave the cell? or Na+ to enter?
K+ to leave the cell.
RMP for skeletal and cardiac muscle
-80 to -90 mV
RMP for neurons
-60 to -70 mV
RMP for smooth muscle
-60 mV
What forces allow us to develop a membrane potential?
- Chemical gradient (diffusion forces)
2. Electrical gradients (electrical gradients)
Diffusion forces
Diffusion forces help to establish a membrane potential. Ions will move from a high concentration to a low concentration.
Electrical forces
Opposite charges will attract, like charges repel. As ions move to either side, a charge will develop and prevent further movement of that ion.
What is the combined force that determines the movement of ions (development of a membrane potential)?
Electrochemical gradient (diffusion force + electrical force).
What is the equilibrium potential (Eion)?
The membrane potential when the electrical and chemical forces exactly oppose one another in direction and magnitude.
It is the electrical force required to oppose the diffusion of the ion across the cell membrane.
Is the equilibrium potential the same as the RMP?
No. Equillibrium potential is for an individual ion.
RMP is is not.
What can we use to calculate the equillibrium potential (E)?
Nerst Equation
Why is the Equillibrium potential for Na+ (+)?
Equilibrium potential–> the electrical force required to exactly oppose the concentration gradient of the ion.
Na+ is more concentrated outside and move in.
Equillbrium potential needs to oppose Na+ movement into the cell so it needs to be (+) because like charges repel.
Why is the E for K+ (-)?
K is more concentrated inside and moves out. This will cause a buildup of - charges inside the cell. Thus, the equillirbium potential will be (-) because it wants to bring K+ back into the cell, and -95mV interior will want to bring it back in.
because opposite charges attract. `
If a cell had only one ion distributed across the membrane, what would the membrane potential be?
equal to that ions equillibrium potential.
What can we figure out from the Nerst equation?
Driving force–> predicts the movement of ions by considering their electrical and chemical forces
How can we derive the driving force from the Nerst equation?
Driving force= [RMP, Vm]- [Eion]
RMP- equillibrium potential
to determine what way the ion will move, compare the answer to the charge of that ion.
Opposite charges attract, like charges repel.
Nerst Equation
(61.5/z) log([X]out/[X]in)
Z= charge of the ion (+/-)
Xout= concentration of the ion outside Xin= concentration of the ion inside
If the concentration of ions is greater inside, than the concentration outside, log will be what?
Negative to drive it in.
If the concentration of ions is greater on the outside, than the concentration inside the cell, log will be what?
Positive, to drive it out of the cell
If the concentration of the ion is the same in and out, what will log be?
0
Ex. You have a RMP of -120mV and K+ has a equillibrium potential of -91mV. How will it move?
-120+91= -29mV is the driving force.
There will be an INFLUX of K+; opposite charges attract.
Ex. RM is -65mV and K+ has a equillibrium potential of -91mV. How will it move?
+26 is the driving force.
Net EFFLUX; like charges repel.
Ex. RM is -85mV and Na+ has a equillibrium potential of +61.5mV. How will it move?
Driving force= -146.5mV
Should be a net influx, but it will not move because the membrane is impermeable to Na+.
What is the driving force of Cl ions across the plasma membrane of a neuron where Cl- interior is 10mM and the Cl- exterior is 100mM?
-3.5mV
Equillibrium potential for Cl-
-66.4
Wants to move out of the cell.
Equillibrium potential for Ca2+
123
Wants to move in the cell
Goldmans equation
allows you to calculate the cells membrane potential considering all ions permeability and concentration.
Is K+ 100% permeable across the membrane?
No. 80-85%.
Is Na+ permeable across the membrane?
1-2%
How does Na+ diffusion contribute to resting membrane?
Barely contributes due to the low permeability.
Increases contribution 5mV
How does Na+/K+ ATP Pumps contribute to the RMP?
Has minimal contribution.
Decreases RMP by 4mV, bringing it back down.
Instead, it indirectly helps to maintain the ion concentration gradients.
How does K+ change the RMP?
1st, think of where it is.
If extracellular K+ decreases, the RMP will decrease.
that will increase our concentration gradient, more K+ will
leave and our RMP will drop down
If extracellular K increases, the RMP will increase.
this will decrease the concentration gradient, keeping K+ inside the cell and increasing RMP
Does a more + RMP make it easier or harder to depolarize?
Easier. Closer to threshold.
Does a more - RMP make it easier or harder to depolarize?
HArder. Further from threshold.
Depolarization
Membrane potential becomes less -
Hyperpolarization
Membrane potential becomes more -
Repolarization
Membrane potential attempts to reach RMP
Polarization
is deviance from 0
What are action potentials?
Large depolarizations that elicits further depolarization and complete reversal of membrane potential across the plasma membrane.
Are the length of action potential the same?
No.
In [motor neurons they’re 2 mseconds]
[Skeletal muscle- 5 mseconds]
[Cardiac ventricles- 200 msec]
Length of AP in motor neurons
2msec
Length of AP in skeletal muscle
5msec
Length of AP in cardiac ventricles
200 msec
3 key properties of AP
- All or none
- Propagate
- Non-decremental
What are graded potentials?
Graded potentials are changes in membrane portential that are small and local. They can be inhibitory or excitatory. They are decremental; dissipate with distance because of K+ leak channels.
What does the strength of the initial graded potential correlate with?
Strength of the triggering event.
Stronger initial GP= stronger triggering event= more channels will open to change the polarity of the membrane
What does a stronger triggering event cause?
More channels will open to change the polarity of the membrane.
The movement of an ion across a membrane is due to
- Chemical grad
- electrical grad
Membrane potential only results for membranes that are selectively permeable bc when electochemical gradient is reached, ions will not be distrib evenly
Why do graded potentials dissipate with distance?
beacause K+ leak channels are always open
What is a AP?
A large depolarization that causes further depolarization and a complete reversal of the membrane potential across the plasma membrane
Does the deviation from resting membrane potential vary between cells?
Yes
What is overshoot?
When we are above 0mV
What are the key players in AP?
- Na+ ions
- K+ ions
- VGNa+ channels
- VGK+ channels
- K leak channels (to a lesser degree)
What are open channels?
Open channels are NON-GATED channels. Ions move through them down their concentration gradient.
Ex. Leak channels
What are gated channels?
Gated channels restrict the movements of ions; thus, they require polarization
Ex of gated channels
VG
LG
signal gated
Mechanically gated
VGNa+ Channel gates
VGNa+ has both an activation gate and inactivation gates.
What are the phases of opening of VGNa+ gates
During rest: Activation gates are closed and inactivation gates are open
Activation: Activation gates open
Inactivation: At 30 mV, inactivation gates closes RAPIDLY (but activation gate is still open); but It cannot open back up until we reach RMP
When do inactivation gates open up again?
When we reach near RMP.
Do VGNa+ channels follow a positive or negative feedback loop?
Positive feedbackloop.
What does it mean that VGNa+ channels follow a + feedback loop
A local triggering event will open some Na+ channels. If the event is big enough, there will be a bigger and wider area of increased MP.
When do VGNa+ channels close?
at +30 mV
What happends during depolarization
- Permeability of membrane to Na+ increases
- VGNa+ channels open RAPDILY
- After a SMALL delay, they close automatically
K+ is leaking out via K+ leak channels
What happens during repoalrization?
- VGNa+ are closed
- K+ is still leaking out
- VGK+ channels are slow to open and increase the membrane permeability to K leaving
What is the differene between VGK+ channels and K+ leak channels
VGK+ channels are selective and have the ability to close.
Why does hyperpolarization occur
VGK+ channels are slow to close.
What occurs during hyperpolarization
We go into a relative refractory period: it becomes more difficult to create an AP.
What are the stages of gate opening and closing in AP
Rest:
Na: Activation gate is closed. Inactivation gate is open.
Threshold:
Na: Activation gate opens
+30mV:
Na: VGNa+ becomes inactive. Inactivation gate closes and activation gate stays open
K: K channel opens
Repolarization:
Na+ channs is rest to closed but capable of opening (Activation gate closes and inactivation gate opens
What is absoluate refractory period?
When Na+ channels are open or the inactivation gate is closed and cannot reopen. We cannot have another AP
What is the relative refractory period?
Some inactivation gates are open and the activation gates are closed.
During this stage, VGK+ channels are slow to close so memrabe becomes slightly more - than RMP.
AP can be initiated, but we need a stronger stimulus.
does K+ permaeability increase and decrease slowly or fast?
Slow.
They are slow to open and slow to close.
During repolarization, what happens to the permeability to Na+?
It decreases RAPIDLY!
PUT IT ALL TOGETHER!
When threshold is reached, what happens?
- Rapid opening of activation gate of LOCAL VGNa+ channels.
- Membrane permeability to Na+ increases LOCALLY
- After small delay, inactivation gates will close locally
- The change in membrane potential will cause MORE Na+ channels to open.
PUT IT ALL TOGETHER!
What happens during depolarization
- Membrane potential will then increase rapidly
- Due to the + feedback loop, there will be a rapid opening of activation gates of Na+ channels.
- Na+ permeability will dominate the membrane
- After minimal delay, inactivation gates will close.
- VGK+ channels will slowly open.
PUT IT ALL TOGETHER!
What happens during repolarization
- Na+ channel inactivation gates are CLOSED.
- VGK+ channels are open
- Permeability to Na+ decreases rapidly and K+ permeability will continue to increase
- membrane potential will begin to drop below resting due to slow close K+ channels.
- potential will drop towards K+ equillibrium potential
Hypokalemic periodic paralysis (HypoPP)
HypoPP is periodic drops in blood K+ levels. When this happens AP will be disrupted.
-MP will decrease and become hyperpolarized because more K+ will want to leave the cell; thus it is harder to reach threshold.
Repolarization occurs more quicly.
in HypoPP, does repolarization occur more or less quickly?
More
Hyperkalemic PP
Excessive blood K+ levels cannot be compensated.
K+ will not want to leave; higher MP leads to prolonged AP and thus, absolute relative refractory periods.
How can we manage patients with Hyperkalemic PP?
mild excersie, K+ wasting diuretics, glucose consumption
what is the effet on refractory periods in a patent with HyperPP?
They will decrease because they will not be reached due to prolonged depolarization
What ar the major movers of ions responsible for generating AP?
VGNa+ channels
