joshua dudman :: [email protected]. 0 mv -80 mv

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Joshua Dudman :: [email protected]

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Page 1: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Joshua Dudman :: [email protected]

Page 2: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

0 mV

Page 3: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

-80 mV

Page 4: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

-80 mV

+++ ++

+

+

--

-

--

-

- +

Page 5: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

-80 mV

[K+] = 135[Na+] = 7[Cl-] = 11A-

[K+] = 2.5[Na+] = 125

[Cl-] = 130A-

+++ ++

+

+

--

-

--

-

- +

Page 6: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Resting membrane potential is independent

of external Na+ concentration

Page 7: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Resting membrane potential strongly depends upon the

external K+ concentration

Page 8: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Why is the resting potential altered by changes in one ion (K+) but not another (Na+)?

Can we quantify how the resting membrane potential depends upon changes in ion concentration?

It depends upon the number and type of ion channels that are open at rest

Page 9: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

So far…

The resting potential is the result of an unequal distribution of ions across the membrane.

The resting potential is sensitive to ions in proportion to their ability to permeate the membrane.

Forget the membrane and consider what factors determine the movement of ions in solution.

Aqueous diffusion

-and-

Electrophoretic movement

Page 10: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

First aqueous diffusion

Diffusion is just the result of thermal agitation.

We can formalize diffusion as:

It is tempting to think of diffusion as a force, however, Einstein demonstrated that it is merely a statistical property of a collection of molecules.

Now electrophoresis

Electrophoresis can be formalized in an analogous fashion.

We can formalize electrophoresis as:

In both diffusion and electrophoresis the rate of movement of molecules, or the flux, is determined by friction with the surrounding solution.

Page 11: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Combining diffusion and electrophoresis

we get:

++

+

+

--

-

- +

Vin

Vout

l

Page 12: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Combining diffusion and electrophoresis

we get:

Two important relationships

Nernst-Einstein Faraday’s constant

What we care about for membrane potential is the current across the membrane

Page 13: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

That oh so famous Nernst-Planck Relationship

When then,

But, we care about equilibrium state. When are we at equilibrium?

Finally, if we integrate across the membrane we arrive at the Nernst Equation

Page 14: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

A little bit more about the Nernst Equation

The general form of the equation in your textbook:

What is the meaning of Ex?

Ex is the potential at which the flux due to diffusion is equal and opposite to the flux due to electrophoresis

What is EK for the cell we showed at the beginning?

Page 15: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

In our cell why was the resting potential -80mV if EK = -100mV?

This cell, as in many other cells in the nervous system, is permeable to more than

one ionic species at rest

How can we quantify the contribution of multiple ionic species?

The Goldman Equation (or the GHK Equation)

Some important details:•Derives from the Nernst-Planck equation and a few

assumptions

•Uses permeabilities rather than conductances

•Cl- is flipped to account for a -1 valence

Page 16: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

There is an important difference between a cell with only potassium flux at rest and one with multiple fluxes

Na+

K+K+ diffusion

K+ electrophoresis

The solution is a pump that maintains the concentration gradient

3 Na+

2 K+

IK + INa = 0 IK = 0

Page 17: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

A neuron can be modeled with an electrical equivalent circuit

When to use:1. To understand the time dependence of changes in ionic

concentration, or conductance state, etc.

2. To easily separate out the current for a specific sepcies of ion

Electrical equivalent ion

channel

Electrical equivalent membrane

Electrical equivalent Na-K

pump

Page 18: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

The complete equivalent circuit

Page 19: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

The passive equivalent circuit

Vout

Vin

IK

INa

Solving for Vrest

1. INa + IK = 0

2. Vin - Vout = EK + IK / gK

3. Vin - Vout = ENa + INa / gNa

4. IK = gK(Vm - EK)

5. INa = gNa(Vm - ENa)

gNa + gK

(ENagNa + EKgK)Vm =

Finally,

Page 20: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

Summary

1. The membrane conducts ions very poorly and allows the separation of ionic species. This results is a potential difference between the outside and the inside of the membrane.

2. The magnitude of the resting potential is determined by the selective permeability of the membrane to ionic species.

3. We can quantify the the magnitude of the resting potential by considering both the diffusive and electrophoretic properties.

4. In order to understand the time dependence and individual contributions of ionic species to the membrane potential it is convenient to use an electrical equivalent circuit.

Page 21: Joshua Dudman :: jtd2001@columbia.edu. 0 mV -80 mV

1. What happens to these considerations during the action potential?

2. Why are the ions collected close to the membrane? What does this mean for the polarization of the bulk solution?

3. How many ions are moving across the membrane?

4. Why is the membrane impermeant to ions?

5. If the membrane is impermeant to ions it means that there is a large energetic barrier that must be overcome. How do ion channels overcome this energetic barrier?

What is the slope of this line?

Some things to think about