Lecture 4 - AP

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Neuronal Signaling: The Whole Story Neuro Lecture 4

Resting Membrane Potential •

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-70mV •

K+ wants to leave the cell - many leak channels available

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Na+ wants to enter the cell - not as many leak channels available

Na+/K+ pump moves Na+ and K+ against their concentration gradients (requires energy) to maintain the RMP •

Responsible for “reseting” the Na+ and K+ gradients

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Requires ATP —- why the brain uses so much energy and oxygen

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http://www.youtube.com/watch?v=P-imDC1txWw

Local Potential •

Neurons can be stimulated by chemicals (NT, H+, etc.), light, heat, or mechanical distortion

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Binding of chemical signal causes Na+ to rush into the neuron resulting in the cell to depolarize

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This flow of Na+ creates a current (flow of charge) within the cell

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Local Potential - occurs in dendrites and cell body •

1. Graded - magnitude varies based on strength of stimuli

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2. Decremental - signal degrades as it moves

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3. Reversible - if enough K+ flows out of the cell, quickly enough, there is no appreciable change in membrane potential

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4. Excitatory (depolarizing) or Inhibitory (hyperpolerizing)

Axon Hillock! or! Trigger Zone

Action Potential •

If the local potential obtains significant depolarization AND travels to the axon hillock, then the AP fires

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1. When Na+ ions arrive at the axon hillock, this region depolarizes

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2. If cell depolarizes to -55mV (threshold), then the voltage gated Na+ channels open very quickly causing Na+ to rush in resulting in more depolarization

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3. At around 0mV, voltage gated Na+ channels become inactivated

Inactivated

Action Potential •

If the local potential obtains significant depolarization AND travels to the axon hillock, then the AP fires

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1. When Na+ ions arrive at the axon hillock, this region depolarizes

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2. If cell depolarizes to -55mV (threshold), then the voltage gated Na+ channels open very quickly causing Na+ to rush in resulting in more depolarization

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3. At around 0mV, voltage gated Na+ channels become inactivated

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4. Voltage gated K+ channels are fully opened when the AP peaks at +40mV causing K+ to leave the cell and repolarize the membrane

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5. Voltage gated K+ channels remain open longer than voltage gated Na+ channels, so the membrane voltage overshoots and becomes slightly more negative than -70mV

AP vs Local Potentials •

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1. All-or-none law - if threshold is reached, the AP fires to maximum amount (+40mV) 2. Nondecremental - the current does not get weaker the farther it travels 3. Irreversible - once threshold has been achieved, there is not stopping it

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1. Graded - magnitude varies based on strength of stimuli

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2. Decremental - signal degrades as it moves

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3. Reversible - if enough K+ flows out of the cell, quickly enough, there is no appreciable change in membrane potential

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4. Excitatory (depolarizing) or Inhibitory (hyperpolerizing)

Refractory Period •

A period of time following the AP that the neuron is resistant to firing an additional AP •

Absolute Refractory - no stimulus of any strength will trigger a new AP •

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All voltage gated Na+ channels are inactivated and have not reset

Relative Refractory - an unusually strong stimulus will trigger an AP •

Some voltage gated Na+ channels have reset

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Occurs during the “overshoot” (hyperpolerization)

Refractory also prevents the AP from moving the wrong direction within an axon

REFRACTORY PERIOD • Voltage gated sodium channel deactivation • ball and chain model • Gates must “reset” between APs • Action potential only moves in one direction • Absolute refractory • no additional APs can fire (all channels inactivated) • Relative refractory • Allows for more AP/unit of time • some channels have reset • larger stimulus is required to send 2nd signal because fewer Na+ channels are available

Inactivated

Websites http://www.youtube.com/watch?v=ifD1YG07fB8 !

http://outreach.mcb.harvard.edu/animations/ actionpotential_short.swf ! !

Signal Conduction along the Axon •

Unmyelinated fibers •

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No insulation so the signal is easily diffused out of the axon and signal may not reach the end

Myelinated fibers •

insulation increases the speed of the signal

MYELIN • Fatty wrapping around axons • 60-80% lipids • improves conduction of electrical signal • think insulation of an electrical wire

OLIGODENDROCYTES • Myelinate neurons in CNS • A single cell can myelinate many axons (up to 50!) • Myelin is inhibitory to axon growth

Schwann Cells • Myelinate neurons in PNS • One cell myelinates one axon • Myelin is conducive to axon growth • Can migrate to CNS after injury

Myelination • Without

myelin! • the signal weakens as it moves down the axon! • With myelin! • The signal does not weaken due to myelin insulation! • at each node of Ranvier the signal is renewed —- no loss of strength

Saltatory Conduction • Improves

conduction by a process known as “saltatory conduction”! • Signal “jumps” between nodes of Ranvier! • https://www.youtube.com/watch?v=i30Bv_E0qAU! • Loss of myelination - multiple sclerosis

Khan Academy Explanation of Saltatory Conduction Watch in Class (8:16 to end) http://youtu.be/ikFUv-gdNLQ?t=8m16s

Watch on your own https://www.youtube.com/watch?v=ikFUv-gdNLQ

Axon Hillock! or! Trigger Zone

Syanpse •

When the AP reaches the axon terminal, voltage gated Ca+2 channels open causing Ca+2 to rush into the cell

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Ca+2 causes vesicles containing neurotransmitter to fuse with the membrane and release their contents into the synaptic cleft

Watch: Start to :55 https://www.youtube.com/watch? v=p5zFgT4aofA

ION CHANNELS

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THERE ARE DIFFERENT TYPES OF ION CHANNELS INCLUDING:

NON-VOLTAGE GATED (LEAK) – Allow passive diffusion of specific ions. Controlled by concentration and voltage gradients across the membrane

LIGAND GATED – Open and close in response to a chemical binding to a receptor in or near the channel. Requires conformational change.

VOLTAGE GATED – Open and close in response to changes in polarization of the neuron. Requires conformational change

Binding of neurotransmitter (NT) to ligand gated channels on the dendrite of the next axon initiates the electrical signal in the next neuron 22

Watch: :55 to end https://www.youtube.com/watch? v=p5zFgT4aofA •

SSRIs

Depression, Anxiety and Schizophrenia https://www.youtube.com/watch?v=InNhDfDfl5c

TRIPARTITE SYNAPSE

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Neurotransmitter •

(1) Broken down in cleft by enzymes

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(2) Taken up by presynaptic neuron and recycled

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(3) Taken up by astrocytes

TRIPARTITE SYNAPSE • Astrocytes act as a sync for neurotransmitters