Resting potential and Action Potential

Chapter 2.2

Review: parts of a neuron

This is the membrane of the entire neuron (soma, axon, dendrites, everything). Semipermeable Water, oxygen, carbon dioxide move freely. Na+, Ca2+, K+, Clmove thru ion channels (protein channels).

This is a cell. For now, lets think of it as a cross section of an axon. There are ions inside and outside the cell. These ions are not equally distributed
ClNa+ ClK+ ClNa+ Na+ AK+ K+ Na AK+
+ A-

Cl-

Na+

K+ Volts
-70 0

ClNa+ Na+ ClA-

Cl-

K+ A-

ClNa+ Na+

Na+ K+ ClA + Na+ K ClANa+ + K

AK+ K+ Na+

A- K+ AClNa+ Cl-

Because of unequal distribution of ions, the inside of the cell is negatively charged compared to outside the cell.
ClNa+ ClK+ ClNa+ Na+ AK+ K+ AK+
+A Na

ClNa+ Na+ ClA-

Cl-

K+ A-

ClNa+ Na+

Na+ K+ ClA + Na+ K ClANa+ + K

AK+ K+ Na+

A- K+ AClNa+ Cl-

The cells membrane has a concentration gradient (different levels of ions inside versus outside) & an electrical gradient (different charge inside versus outside).

The cells membrane is polarized

Important Concept: Polarized

Different inside vs. outside (-70 mV) As cell becomes less negative, it is depolarized (less polarized) As cell becomes more negative, it is hyperpolarized (more polarized)

-70 mV is the resting potential. Less negative than -70 is depolarized. More negative than -70 is hyperpolarized.
Na+

Volts
-70 0

ClK+
-50 mV -70 mV time

How could we depolarize the cell? How could we hyperpolarize the cell?

How is the resting potential maintained?

Selective Permeability of the membrane: some molecules pass more freely across the membrane than do other molecules; controlled by channels
At rest: H2O, CO2, O2 pass freely K+ and Cl- ions pass slowly No net change in these ions Na+ channels are closed* Na+/K+ pump (next slide)
*certain types of stimulation cause the Na+ channels to open

Sodium-Potassium Pump

Acts to maintain proper concentrations of Na+ and K+ Needed for maintaining resting potential and for recovery from an action potential. 3 Na+ out for every 2 K+ in, so more positive on outside

(Midway) Summary
Ions are unequally distributed across the membrane of a cell. The membrane is polarized. The membrane has a resting potential of -70 mV. The semi-permeable nature of the membrane, and the Na+/K+ pump, maintain the resting membrane potential.

The Action Potential

Electrical impulse down an axon. Depends on sodium (Na+) and potassium (K+) moving thru channels in the axons membrane

What forces could move ions into and out of cells? Concentration gradient: ions flow
from areas of high concentration to low concentration

Electrical gradient: ions flow to areas

of opposite charge
negative to positive, positive to negative

If a potassium channel opens, what will the concentration gradient (diffusion) try to force potassium to do?

-70mV
K+

If a potassium channel opens, what will the electrical gradient try to force potassium to do? If a sodium channel opens, what will the concentration gradient (diffusion) try to force sodium to do?

Na+

Cl-

If a sodium channel opens, what will the electrical gradient try to force sodium to do?

What happens if sodium rushes into cell?

-70mV
K+

A. Cell becomes depolarized (less negative) B. Cell becomes hyperpolarized (more negative) C. Nothing

Na+

Cl-

What happens if potassium rushes out of a cell?

-70mV
K+

A. Cell becomes depolarized (less negative) B. Cell becomes hyperpolarized (more negative) C. Nothing

Na+

Cl-

So, why do we care about ion movement??

That is how action potentials work!

This ion movement is the action potential

Propagation of The Action Potential

Threshold is reached at the axon hillock Voltage-gated Na+ channels open Na+ enters the cell What forces bring in Na+?? What happens to the voltage of the cell when Na+ enters??

Propagation of The Action Potential

Now, VGNaCs close and VGKCs open K+ leaves the cell What forces push out K+?? What happens to the voltage of the cell when K+ leaves??

Propagation of The Action Potential

So much K+ exits the cell, that it becomes hyperpolarized! When it reaches resting membrane potential again, it can conduct another action potential That period of hyperpolarization is called the refractory period

 Sodium in Potassium out Refractory period (The neuron cannot fire another action potential until it is back up to resting potential) and repolarization

Sodium in Potassium out -50 mV -70 mV time Refractory period

Threshold
*The critical level of depolarization that must be achieved to trigger an action potential is called the threshold.

-50 mV -70 mV time

Propagation of The Action Potential

When Na+ entered cell, it flowed down axon, depolarizing the neighboring membrane and thus opening other VGNaCs What happened when those VGNaCs opened? Then what, then what, then what??

Action Potential Voltage-dependent V-dependent Na+ channels close Na+ channels open* (cannot reopen until membrane is back to Transmitter-dependent Na+ channels open
resting potential)

Voltage-dependent K+ channels open (less sensitive than V-D Na+ ch;

K+ leaves b/c chemical & electrical gradients)

Voltage-dependent K+ channels close Na/K pumps repolarize

Summary: The Action Potential

The Action Potential is the signal that conveys information over distances in the nervous system. The action potential is a rapid reversal of the situation at rest --for an instant, the inside of the membrane becomes positively charged relative to the outside. Action potentials are all or none. The frequency and pattern of action potentials is the code used by neurons to transfer information from one location to another. All of this occurs at the nodes of ranvier, between the segments of myelin.

Propagation of the action potential depends on:

Diameter of axon Insulation (myelin)

Myelin and Saltatory Conduction

Voltage-gated Na+ channels are concentrated at the Nodes of Ranvier.

In Myelinated axons, action potential can jump down axon. Much faster. Allows long distance rapid communication
Passive conduction that diminishes but has enough strength at next node for another AP to occur

Action potential

Saltatory conduction energy & speed

Fun fact
Anesthetics prevent APs Local Anesthetics (novacaine, xylocaine) attach to Na+ channels & prevent Na+ from entering cells General Anesthetics (ether, chloroform) decrease brain activity by opening K+ channels wider than usual

Study Questions
What ions are important in the action potential? When the cell is at rest, which ions are most highly concentrated inside of the cell, and which ones are most highly concentrated outside of the cell? Understand the forces working on the ions (electrical gradient and concentration gradient). What is a voltage-gated channel? Where are they? Understand the steps of the action potential, and how one leads to the next. How is an action potential started and propagated? What ion enters first? Thru what type of channel does it enter? What forces drive it inside? Why does that channel close? What channel opens next? What ion moves thru that? What forces drive that ion? Etc etc. Terms to know and understand with regard to neurophysiology: polarized, depolatization, hyperpolarization, repolarization, resting potential, threshold
With regard to those last 2 terms, What voltage is resting potential? What voltage is threshold? Where must threshold be reached for an action potential to occur?

What is the sodium/potassium pump? What does it do? What purpose does it serve? What is the purpose of myelin? What happens at the nodes of Ranvier? What is saltatory conduction? What does it mean that an action potential is all or none?

 The rest of the slides contain additional (non-testable) material, for inquiring minds Or additional slides on what we just covered, for clarification.

Multiple Sclerosis: A Demyelinating Disease

MS causes weakness, lack of coordination, impaired vision and speech. It is also characterized by remissions and relapses that occur over many years. MS attacks the myelin sheaths of axons in the brain, spinal cord, and optic nerves. The name comes from the Greek word for hardening which describes the lesions that develop around bundles of axons; and the sclerosis is multiple because the disease attacks many sites at the same time. The lesions can be viewed by MRI. However, neurologists have been able to diagnose MS by measuring changes in conduction velocity. One test involves visual stimulation with a checkerboard pattern and measuring the elapsed time until an electrical response occurs in scalp electrodes. The response is slowed in people with MS because of the slowing of the conduction velocity of the optic nerve.

The effects of toxins on the sodium channel. Tetrodotoxin (TTX): This toxin clogs the pore by binding to a site on the outside of the channel. Originally isolated from the puffer fish. Another channel blocking toxin is saxitoxin. This toxin is produced by dinoflagellates and can be concentrated in clams, mussels, and other shellfish that feed on the protozoa. A dinoflagellate bloom causes what is known as a red tide. Eating shellfish during a bloom can be fatal. Other toxins, such as batrachotoxin (from the skin of a Colombian frog) causes the channels to open inappropriately (i.e. at more negative potentials) and stay open much longer than usual. Other toxins with similar mechanisms come from lilies (veratridine) and buttercups (aconitine). Some toxins, such as those from scorpions and sea anemones, disrupt channel inactivation.

Qs from other class

How fast does an action potential occur?
~3 msec, including refractory period

How does caffeine work? How exactly do voltage-gated Na+ (and K+) channels work?
Next slide

-50 mV -70 mV time

Voltage-gated Na+ channel

Sodium Channel Structure Created from a single long polypeptide 4 domains, I-IV, that form the pore 6 transmembrane alpha helices S1-S6

The sodium channel has a pore loop (b/t S5S6) that functions as a selectivity filter making it 12X more selective for Na+ than K+. (Similar to the potassium channel)

The channel is gated by a change in voltage across the membrane. The voltage sensor resides in the S4 segment. Positively charged amino acid residues are regularly spaced along the coils of the helix. Depolarization pushes the S4 away from the inside of the membrane causing a conformational change that opens the gate.

Resting Potentials of Neurons

The Membrane of a Nerve Cell Maintains an Electrical Polarization

outside (+)

The cell has a concentration gradient: difference in distribution of ions between the inside and outside of a membrane

Therefore
The cell is polarized: at rest, an electrical gradient is maintained across the plasma membrane (negative charge is greater inside the cell)

inside (-)

The cell has a resting potential: difference in voltage across the membrane of a cell (~ -70 mV) a rest.

How do the concentration gradient and electrical gradient affect ion movement?
Forces
Concentration Gradient Electrical gradient

E Less Na+ inside More K+ inside

More negative inside