Lectures 6 & 7

What is the conductance before threshold?

0

Conductance peaks around

0mv

What determines the slope of an action potential?

1. Concentration of ions 2. Types of ion channels present

Ek+ = -80, Vrest= -40 What flow?

Always remember think about Vm. So Vm>Ek+ so outward flow. K+ flows outside.

Compared to equilibrium at 19, equilibrium at 40 will?

Cannot tell without O/I ratio since you don't know if you are multiplying with positive or negative number

How to change threshold?

Change properties of voltage gated channels

How to change threshold?

Change property of channel

What has more effect: a. Pumps b. transporters c. channels

Channels

Magnitude of DF for Na+ does what as we get to the equilibrium potential?

Decreases

Channels always peak at 0mV

False, that is a property of the channel

At Vrest.. only one of the channels is open.

False. At Vrest, both of the channels are open

How to account for valence in goldmann equation?

Flip the negative ions

(b) What must be changed in order for a 10 fold change in [K+] to change Vm by 58 mV?

In reality, it is very difficult to achieve the precise 58 mV change in VM. This is because the 58 mV change pertains to the equilibrium potential of a single ion, not to Vm. Vm is affected by the concentrations and permeabilities of multiple ions (K+, Na+ and Cl- being the most influential)

Early on in action potential

Increased permeability of Na+

(b) How might running a fever (i.e. increased temperature) affect the function of the nervous system?

It suggests that when you have a temperature (and if nothing else changes) the Vm your neurons will decrease, making it more difficult to fire an action potential. In reality, many things in the body and the neurons compensate and try to prevent this from happening.

At rest, K+ will have larger effect because?

It's the one that comes to equilibrium

During the falling phase,

K+ leaves the neuron

Increasing permeability of K+ will give what?

More outward current

During the rising phase of AP

Na+ enters the neuron

During undershoot...

Na+ flowing out determines the Vm towards ENa+

AP peak goes to E of?

Na+, means Na+ going in.

Does Nerst equation tell you how membrane potential changes with ion concentration?

No

Do you need to know permeability to figure out direction?

No Na+ CG: O-i EG: O-i so inward current

(d) Does the Vm change 10 fold with each 10 fold change in PNa+ or PK+? Why or why not?

No, as documented above, a 10 fold change in Px causes less than a 10 fold change in Vm. This is because there are many types of ions that affect Vm. It might be possible through some combination of decreasing Pk and increases PNa, but I haven't tried that.

For K, can you can figure out direction from CG and EG, of from DF?

No, need to know Ek and Vrest

Does the K+ face a different threshold?

No, same threshold, but the K+ channel takes longer to change shape

Is the closed channel same as inactivated?

No, the pore is open in inactivated channel

Goldmann + ion is

O/i

ENa at 100?

Outward flow happens. So Na+ never goes above ENa+

Name the phases of an action potential (e.g. rising phase) and describe the relative permeability and direction of the current for Na+ and K+.

Rising phase: permeability for Na+ > K+, Na+ inward current, K+ outward Overshoot: permeability for Na+ >>K+, currents in same direction as rising phase Falling phase: permeability for K+>Na+, current direction same as for rising phase Undershoot: permeability for K+>>Na+, K+ going out at the beginning of the undershoot until the nadir (bottom of curve) is reached close to EK, then K+ goes in until returns to Vrest

If Na+ channels took 10x longer to open...

The AP would be broader

What happened around the same time that the Na+ channels begin to close?

The K+ channels begin to open

(a) Using the Goldman simulator and the default setting for temperature, change the [K+]o or [K+]i by 10 fold. Does Vm change by 58 mV?

The change is close to, but exactly 58 mV (e.g. start Vm= -59.2 mV. Increase [K+]o from 10 to 100 and Vm= -2mV, a difference of 57.2 mV. Decrease [K+]i by 10 fold and Vm= -13.8 mV, a difference of 45.4 mV).

Goldmann - ion is

i/O

Increasing inside concentration of Cl- in goldmann will?

increase the Vm

If pos. and O/I > 1 Vm will? regardless of?

increase, regardless of permeability

K+ has a much higher concentration

inside

For Na+ increasing the permeability will give more?

inward current

Cl- is flowing inward. It's vm is?

inward flow of neg ion is same as outward flow so Vm>ECl-

positive current is?

ions flowing in

negative current is?causes?

ions flowing out. Hyperpolarization.

Ion channels allow

ions to diffuse down concentration gradient, are selectively permeable to certain ions

As k+ leaves the neuron,

it becomes more and more negative - hyperpolarizes

The positively charged Na+ causes the neuron to become

less and less negative (depolarizes)

Increasing amount of current above threshold means?

more action potentials

Na+ has a much higher concentration?

outside

Vm>0 is? Vm> Vrest?

overshoot phase. Deploarized.

pumps and transporters

require energy, are active

Na+ is important in determining

the peak of the Action potential

Threshold is when...

your voltage-gated channels start to open

During the overshoot phase..

Vm becomes positive

(b) What happens when PK+ is changed from 5 to 50 to 500?

Vm goes from -48.1 to -57.5 to -61.1 (i.e. as PK increases Vm decreases)

a) Using the Goldman Simulator, determine how the Vm changes when PNa+ is increased from 5 to 50 to 500.

Vm increases from -51.6 to -16.9 to 31.0 mV (i.e. as PNa increases Vm increases).

As temperature decreases....

Vm increases since the Log part of the goldmann equation becomes negative

ENa+ = 50, Vrest = -40 What flow?

Vm<ENa+ so inward flow. Na+ comes inside.

Need to know what to determine direction?

Vrest

When does the overshoot phase occur?

When Vm>0

Active transporters move ions

against concentration gradient , they create ion gradients

Na+ plays a major role in determining the?

amplitude of AP

passive changes occur..

before the channels open

For action potential to occur, you need

change in permeability of Na+ and k+ at different time points.

Ion flow is largely determined by

conductance since DF doesn't change that much

(a) Using the default setting on the simulator, experiment with changing the temperature. How does increasing the temperature affect Vm?

As temperature decreases, Vm increases (e.g. at 37 deg Vm=-59.2, at 19 deg Vm= -55.8)

(a) Using the Nernst Equation, How does Ek change when extracellular K+ changes from 5 to 50 mM?

Assuming temp = 19 deg. Celsius, a 10 fold increase in [K+]o will increase EK by 58 mV

Describe 2 mechanisms that have evolved to enable long distance propagation of an action potential down an axon.

Axons can increase in diameter and/or be myeltinated. In future lectures we'll see that the fastest axons are large in diameter and myelinated. Myelination is only found in invertebrates.

(2) What might happen to an axon if the voltage-gated Na+ channel were able to close, but did not inactivate?

The normal pattern for the Na+ channels is: 1) At threshold Vm, the channel opens 2) After a relatively short period of time, the Na+ cannel inactivates (i.e. the "inactivation loop" of the channel protein moves into place and prevents the channel from reopening). As long as the channel inactivation loop is in place, the channel cannot open, regardless of the Vm. During this period, the channel is said to be "refractory" to activation. The duration of this refractory period sets the minimal interval between APs. 3) After some time, the inactivation loop moves pout of the channel and the channel rests to the "closed" state and can now be activated/open at Vm above threshold. Answer: If the channel closes, but does not inactivate, there will be no refractory period and the time between APs could be shorter.

(1) What would happen to the shape of the action potential curve (membrane potential vs. time) if the voltage gated Na+ channels took 10 times longer to inactivate than normal?

The rising phase of the AP is due mostly to Na+ influx and the falling phase to K+ efflux (i.e. going out of the cell). The Na+ channels open and inactivate relatively quickly (inactivating is time dependent and will happen even above threshold Vm). The K+ channels open slowly and stay open (as long as the Vm is above threshold). The reason that the current changes direction in the overshoot phase is that most of the Na+ channels are inactivated while most of the K+ channels are open. Answer: If the Na+ channels take longer to close, the AP would last longer (i.e. the overshoot phase would take longer to change direction.)

The further Ex is from Vm,

The stronger the DFx

(c) What does changing PNa+ have the opposite effect of changing PK+?

This has to do with the relative outside vs. inside concentrations, the equilibrium potentials and the driving force on Na+ and K+. At the default conditions, the EK+ = -61.5 and ENa+ = 61.5 mV (in these idealized conditions these values are equal and opposite, but this is rarely the case in the real world). The greater the permeability for an ion, the closer Vm is to the Ex for that ion. So, increase PNa+ and the VM gets closer to +61.5mV and increase PK+ and Vm gets closer to -61.5 mV.