LECTURE 2 Action Potential

what is the resting potential of a neuron

-70mV

Receptor Potentials

Receptor potentials are changes in membrane potential that occur where a stimulus is actually received. receptor potentials occur at sensory receptors, which means we have receptor potentials for sense of smell, taste, vision, auditory processing, touch Example: touch receptors in hand, receptor potential when you press down on a hard surface The stimulus causes the opening of ion channels

Performance Enhancement Through Myelination

Repeated activation of a nerve increases myelin Practice enhances myelination in the brain and on peripheral nerves BEING ACTIVE practice enhances brain neurons = can do things with eyes closed

Motorneuron Axon: The link between brain and muscle

The motor neuron axon completes the connection between the spinal cord and the muscle fibers (lower motor neurons). A reduction in the ability of a motor neuron to transmit an action potential frequently underlies multiple neurological disorders (myelinated) Example: ALS, motor neurons are deteriorated so they cant fire action potentials

What Happens during the falling phase of the action potential

cell is depolarized (LESS NEGATIVE) Voltage-gated Potassium channels open (30mV) Potassium LEAVES the cell because the cell is now more positive than negative. Because it's positive, potassium leaves the cell because like charges repel. When potassium leaves, this causes repolarization. (falling phase of action potential) During repolarization the cell overshoots its original resting membrane potential becoming "hyperpolarized". Hyperpolarization is important because it keeps the neuron from responding to weak stimuli briefly. Potassium channels restore the electrical conditions- BUT not ionic conditions (concentration is different) ... this means the cell is becoming more negative again because K+ leaves the cell but the concentrations are still diff The ionic conditions (concentration) are restored by the sodium/ potassium pump! pushes out 3 sodium ions and pulls in 2 potassium ions Membrane potential is now normalized to resting at -70 mV

what is contained inside of the cell /neuron

a lot of potassium little sodium little chloride negatively charged proteins/anions

g-protein couple receptor

a neurotransmitter binds to the surface of a membrane bound protein/receptor --> intracellular events lead to intracellular signaling mechanism that activates from inside of the cell --> the sodium channel will open up and allow sodium to flow through

voltage sensor

changes shape when membrane potential depolarizes

What is an Action Potential?

action potential: Is what happens when neurons 'fire' or 'spike' ALL OR NOTHING action potential is always DEPOLARIZING action potentials occur after a neuron has reached "Threshold" and then it Propagates along an axon

what does it mean when we say receptor potentials are graded responses ?

amplitude of stimulus = amplitude of response as you increase size of stimulus, you increase size of receptor potential, then if you cause enough depolarization you'll fire an action potential if you increase stimulus more, receptor potential gets even bigger, as result of depolarization you'll have more action potentials being fired bigger stimuli = bigger responses = more action potentials smaller stimuli = smaller responses = less action potentials

Current Flow Demyelinated Axon: how does Cooling restore function

demyelinated sections can fill in with sodium channels so instead of stopping conduction, this segment will act like a non-myelinated neuron would Cold temps allow NA+ channel to stay open longer so the action potential can travel further down the axon patients w MS will wear cooling vests like ice vests, or circulation of fluid, by cooling down core temp you cause channels to stay open longer and have a better time conducting information down length of axon

action potentials

how neurons communicate over long distances sometimes neurons have to communicate over long distances, this happens through axonal production an action potential is what happens when a neuron "fires"

conduction speed why do axons conduct at slower/quicker speeds?

if the diameter of the axon is thicker, the impulses / action potentials are received quicker because there is less electrical resistance if the diameter of the axon is thinner, the impulses / action potentials are received slower because there is more electrical resistance

what happens when the myelin sheath deteriorates

muscles begin to lose their ability to respond to the brain's commands to move muscles brain receives fewer sensory signals from the rest of the body, resulting in an inability to feel textures, heat, pain, and other sensations. brain may receive inappropriate signals that result in tingling, "crawling-skin," or painful sensations. arms and legs are most vulnerable because they are furthest away, then it progresses upward

Myelinated Axon

myelin sheath is an insulating layer that forms around some axon lengths made up of protein and lipids have Sodium channels that are located at nodes of ranvier / between nodes sodium channels are not continuous along the axon action potential is generated, maintains the charge for some distance until it reaches next node, when it reaches that node the action potential is regenerated and maintains its charge till the next... they skip segments and then cause depolarization in each node they reach depolarization --> maintain charge --> travel to next node REPEAT Myelin allows electrical impulses to transmit quickly along the axon

Oligodendrocytes

myelinate the axons of the central nervous system

at rest, does the inside of cell have negative or positive resting membrane potential

negative there is a separation of charge when the cell is at rest (polarized)

what effects a cells permeability?

neuron receives message from another neuron a receptor picks up stimulus in your environment when change happens within the internal or external environment, this causes change in the cell membrane which can effect its permeability (solutes/ions will be able to move)

Ligand-gated ion channels

neurotransmitter that is carrying information binds to a protein --> cell receives information --> the channel will open up allowing sodium ions to pass This can begin depolarization of cellular membrane cell is normally polarized at rest, then a signal stimulates the cell, allows ions to flow through, and that starts the process of depolarization (membrane potential is decreasing and the cell is becoming more similar than different)

synaptic potentials

occur at synapses when one neuron receives input from other neurons neuron to neuron communication Can be depolarizing (excitatory) or hyperpolarizing (inhibitory) to the cell Thousands of neurons can all synapse onto a single neuron to excite it or inhibit it in small increments small increments of inhibition or excitation are called synaptic potentials small increments change the membrane potential of a neuron making the neuron more or less likely to fire If enough excitatory inputs are 'summed up' they can push the membrane potential past threshold and cause an action potential

threshold

point of no return about -55 mV when neuron passes threshold, it will fire action potential no threshold no action potential CELL MUST DEPOLARIZE TO THRESHOLD

Temporal Summation

repeated rapid fire excitation from one input summates to reach threshold single neuron receives input from one other neuron, the neuron is giving input at rapid fire, a lot of excitatory postsynaptic potential, this causes enough depolarization to cause the neuron to fire an action potential pre-synaptic neuron is stimulating the post-synaptic neuron that fires BRIEF

spatial summation

simultaneous excitation of a neuron from multiple sources add up to reach threshold Example: Neuron receiving input from three diff neurons. The input from the three neurons isn't happening fast, but its happening in one location. This provides enough depolarization for the receiving neuron to pass threshold and fire an action potential pre-synaptic neurons are stimulating the post-synaptic neuron that fires

Action potentials are generally initiated by

sodium influx into the neuron

What happens during the rising phase of the action potential?

start at -70mV Local potentials drive membrane -70 mV up to -55 mV Cell reaches threshold. Voltage gated sodium channels pop open causing DEPOLARIZATION depolarization: have a ton of sodium entering the cell (cell is more similar than it was different) Na+ influx drives the interior of the cell membrane up to about +30 mV. Peak of action potential causes voltage gated Na+ channels to close. Depolarization is now complete. refractory period: Na+ channels can't open again! (Absolute Refractory Period) K+ channels open next...

ions have a tendency to move from areas of high concentration to low concentration, but at rest, why can't they move?

they can't do this very easily because of the membrane that is separating intracellular from extracellular space (semi-permeable, only allows certain ions to pass under certain circumstances)

neuron threshold

this is the level of depolarization that needs to occur before they fire an action potential- this is about -55 mV.

How Do Voltage Gated Sodium Channels Work?

through diff subunits Voltage Sensor Gate Ion Selectivity Filter Inactivation Gate

how do you depolarize a neuron?

to change a neuron's membrane potential and cause depolarization you must disturb the membrane potential at rest / disturb the neuron at rest ways to do disturb membrane potential and cause depolarization: Receptor potentials. Synaptic potentials. Local potentials.

Unmyelinated Axon

unmyelinate = no myelin sheath voltage gated sodium channels are continuous along the entire axon when cell is stimulated membrane potential changes, reaches threshold, sodium channels open, and causes adjacent sodium channels to open up as well, so all cells are depolarizing, this allows the action potential to constantly be regenerated down the entire axon DOMINO EFFECT, going in ONE direction the action potential will travel in one direction because of the refractory period this method takes time because it takes a while to open up all channels action potential propagation = slower

Myelinated vs Unmyelnated Conduction Speed

unmyelinated axons: sodium channels have to open up one-after-another allllllllllllll the way down the axon- this takes time Myelin allows the action potential to spread further before more channels open up-this is fast Myelin: enhances conduction speed by skipping over large lengths of axon

Aging and Peripheral Nerve Function

As we age, myelinated fiber density declines and it takes a longer amount of time for nerves to send signals down the axon older athletes lose the myelin, become slower

Summated Local Potentials Can Lead To

Action Potentials

How does Potassium Leave the cell?

After the cell has depolarized- voltage gated potassium channels open selective to potassium (only allow potassium through) SLOWER than the voltage gated sodium channels- so they stay open longer and this leads to hyperpolarization. Restore resting potential but not ionic balance.

What Would Happen If a Normally Myelinated Axon Was Demyelinated?

Diphtheria toxin -bacteria secretes a toxin that inhibits the proteolipid that is necessary for the maintenance of myelin -myelin sheaths begin to deteriorate, signals can't propagate down the length of myelinated axons Guillain-Barre disease -viral infection, the immune system gets confused about what it should attack and our body starts to destroy the myelin sheath that surrounds the axons -myelin sheath is destroyed and cant propagate action potentials down length of axon Multiple sclerosis -most common demyelinating disease of the central nervous system immune system attacks the myelin sheath / cells that produce / maintain it. This causes inflammation and injury to the sheath and nerve fibers that it surrounds and may result in multiple areas of scarring (sclerosis)

Ohm's Law

I=V/R As resistance (R) INCREASES, current (I) flow DECREASES As resistance (R) DECREASES, current (I) flow INCREASES

How Does an Action Potential start?

Initial depolarization (can happen through local potential or synaptic potentials) causes ligand or mechanical NA+ channels to open up to let sodium in (because change in voltage, this made the protein/channels to change shape, allowing sodium to come in) When enough NA+ channels open up, membrane potential reaches threshold opening up voltage gated sodium channels! massive efflux of sodium into the neuron

Where Does an Action Potential Start?

It varies between neuron types and can shift in location on a neuron Axon Hillock? Axon Initial Segment?

gate

Opens when voltage sensor reaches threshold (when neurons membrane has change in potential where it reaches -55mV the voltage center will cause gate to open up)

Inactivation Gate:

Limits amount of time the channel stays open. Gate open for brief period of time. The gate plugs the hole and stops influx of sodium, so now sodium channel cant be activated even if we have change in membrane potential protein needs to go through different types of processes to reset itself to be able to re-fire and action potential

Sometimes blocking action potentials is clinically useful!

Local anesthetics prevent the transmission of sensory information to the CNS They typically block voltage-gated sodium channels (e.g. lidocaine, novacaine, cocaine) prevent pain through transmission

Local Potentials

Small change in the membrane potential of a neuron that occurs in the area around where a sodium channel has opened. Becomes weaker as it spreads away from the site of stimulation Under the right conditions, if you have enough repeat stimulation, local potentials can add up and cause an action potential... they do this through summation

What would happen if you could disrupt sodium channels?

Sodium channel blockers: tetrodotoxin (TTX) : made by puffer fish Saxitoxin: Produced by algae. Eaten by shellfish, then we eat the shellfish and can get poisoned both are sodium channel blockers ; they plug holes where sodium passes through in the voltage gated sodium channels, this prevents action potentials! Symptoms: tingling loss of muscle control in arms and legs difficulty breathing if you consume too much = cardiac arrest

How are action potentials propagated under normal conditions? How does it get from one end of the neuron to the other?

Some action potentials have a very long way to travel example: spine to toe It depends on whether a neuron contains Myelinated or Unmyelinated axons

what happens when a neuron receives information

it begins to change its membrane permeability, which can lead to an action potential

ion selectivity filter

lets only sodium in. When gate opens it allows sodium to go from outside of neuron to inside of neuron, but this selectivity filter only allows sodium in.

How Can the Membrane Change Permeability?

ligand-gated ion channels g-protein coupled receptors

Axon Initial Segment

more conductive than other regions of the neuron located on the axon hillock and there is a very high density of voltage gated sodium channels here that make it a very excitable region of the neuron its an optimal spot to start up action potential process

explain the events of the rising and falling phases of an action potential

starting at -70mv, cell is polarized (different/ cell negative) local potential/some stimulus changes membrane potential drives the cell from -70mv to -55mv when the cell reaches its threshold (gate threshold) at -55mv (point of no return), action potential is fired, sodium channels open and causes depolarization of the cell influx/depolarization causes interior of the cell to eventually reach +30mv AKA peak of action potential so NA channels close and depolarization is complete AKA CELL MORE POSITIVE NOW there is a refractory period where sodium channels will not be able to open up when depolarization is complete, potassium channels open, potassium(K+) slowly LEAVES the cell (LIKE CHARGES REPEL) (this gate is open longer for hyper-polarization) leaving of potassium causes re-polarization as potassium LEAVES the cell, it restores the electrical conditions and brings the cell into a state of hyper-polarization the sodium/potassium pump then restores the ionic conditions and brings the cell back to polarization / cells resting state

Schwann cells

supply the myelin for the peripheral nervous system