Excitable Cells: Graded Potentials

What did Santiago Ramón Y Cajal do

• Used stains to trace neural pathways

  • Showed pathways are made of distinct neurons (not continuous tubes as was commonly believed)

  • Demonstrated separate neurons are connected by synapses

Neuron Receptive Segment

Cell body

• Binding of neurotransmitter released from presynaptic neurons; production of graded potentials

Neuron initial segment

Axon Hillock

• Summation of graded potentials; initiation of action potential

Neuron conductive segment

Axon

• Propagation of action potentials

Neuron Transmissive segment

Axon terminal

• Release of neurotransmitter

Nerve Growth Factor (NGF)

Protein secreted by a gland, muscle, or glial cells and picked up by the axon terminals of neurons

What does Nerve Growth Factor (NGF) do

Prevents apoptosis in growing neurons

Enables growing neurons to make contact with targets

Who isolated Nerve Growth Factor (NGF)

Rita Levi-Montalcini in the 1950s

The receptive segment has what kind of channels

Chemically gates cation channels, Chemically gates potassium channels, chemically gated chloride channels

The initial segment has what kind of channels

Voltage gated sodium and potassium channels

The conductive segment has what kind if channels

Voltage gated sodium and potassium channels

The plasma membrane of the neuron has what kind of channels

Sodium potassium pump, and Sodium and potassium leak channels

What happens to an electrical signal when it reaches the end of an axon

The electrical signal can go no further

When an electrical signal reaches the end of the axon what does it trigger

The release of a chemical neurotransmitter

It also stimulates a new wave of electrical activity in the next cell (across the synapse)

What are the synapses between neurons

• First neuron in the signal path is the presynaptic neuron

  • Release the neurotransmitter

• The second neuron is the postsynaptic neuron

  • Responds to the neurotransmitter

A presynaptic neuron may synapse with what

A dendrite, neurosoma, or axon of a postsynaptic neuron

A presynaptic neuron may synapse with a dendrite, neurosoma, or axon of a postsynaptic neuron to form what

Axodendritic, axosomatic, or axoaxonic synapses

A neuron can have an enormous number of synapses because

The spinal motor neuron covered by 10,000 axon terminals from other neurons

• 8,00 ending on its dendrites

• 2,000 ending on its neruosoma

In the cerebellum of the brain, one neuron can have as many as [blank] synapses

100,000 synapses

The synaptic cleft

Gap between neurons

Who discovered the synaptic cleft

Santiago Ramón Y Cajal

What was the first known neurotransmitter

Acetylcholine

Who discovered Acetylcholine

Otto Loewi

An axon terminal of a presynaptic neuron contains synaptic vesicles that contain

Neurotransmitter

• Many vesicles are docked on release sites on plasms membrane ready to release neurotransmitter

A postsynaptic neuron membrane contains

Neurotransmitter receptions

• Ligand-gated ion gates open when neurotransmitters bind to them

Why are synapses variable

• Some neurotransmitters are excitatory, other inhibitory, and sometimes a transmitter’s effect differs depending on the type of receptor on the postsynaptic cell

• Some receptors are ligand-gated ion channels; others act through intracellular second messengers

What are three kinds of synapses

1. Excitatory cholinergic synapse

2. Inhibitory GABA-ergic synapse

3. Excitatory adrenergic synapse

Generation of EPSP steps

1. Neurotransmitter is released from a presynaptic neuron

2. Chemically gated cation channels open

3. [blank] is established

4. [blank] moves toward the initial segment

Generation of IPSP steps

1. Neurotransmitter is released from a presynaptic neuron

2. Chemically gated potassium or chloride channels open

3. [blank] is established

4. [blank] moves toward the initial segment

How many neurotransmitters have been identified

More than 100

What are the four major chemical categories of neurotransmitters

Acetylcholine

Amino Acids

Monoamines

Neuropeptides

What is acetylcholine formed by

Acetic acid and choline

Where does Acetylcholine (ACh) work

Neuromuscular junctions, most synapses of autonomic nervous system, retina, and many parts of the brain; excites skeletal muscle, inhibits cardiac muscle, and has excitatory or inhibitory effects on smooth muscle and glands depending on location

Where does Glutamate work

Cerebral cortex and brainstem; accounts for 75% of all excitatory synaptic transmission in the brain; involved in learning and memory

Where does Glycine work

Inhibitory neurons of the brain, spinal cord. and retina; most common inhibitory neurotransmitter in the spinal cord

Where does GABA work

Thalamus, hypothalamus, cerebellum, occipital loves of cerebellum, and retina; the most common inhibitory neurotransmitter in the brain

What are some amino acid neurotransmitters

Glycine, glutamate, aspartate, and GABA

What are some monoamine neurotransmitters

Catecholamines, epinephrine, norepinephrine dopamine, histamine, ATP, and serotonin

What are monoamines syntehsized from

Amino acids

What are some examples of neuropeptides neurotransmitters

Cholecystokinin and substance P

What are neuropeptides made from

Chains of 2-40 amino acids

Where are neuropeptides stored

Secretory granules

Examples of Purines neurotransmitters

Adenosine and ATP

Example of gas neurotransmitters

Nitric oxide (NO) and Carbon monoxide (CO)

What makes gas neurotransmitters different

• They are synthesized as needed (not stored in synaptic vesicles)

• Diffuse out of axon terminal (not released by exocytosis)

• Diffuse into the postsynaptic neuron (don’t bind to a membrane surface receptor)

Cholinergic synapses use

Acetylcholine (ACh)

How do Excitatory Cholinergic synapses work

1. Action potential depolarizes the axon terminal, and opens voltage-gated calcium channels

2. ACh diffuses across the synaptic cleft, and binds to postsynaptic receptors

3. Entry of sodium causes depolarizing postsynaptic potential

   1. If strong enough, depolarization spreads to the trigger zone, raises the membrane potential up to threshold

   2. Action potential is triggered in the postsynaptic cell

ACh receptors are what kind of channels

Ligand-gated ion channels that open to allow sodium and potassium across the membrane

GABA receptors are what kind of channels

Chloride channels

• Chloride current hyperpolarizes the postsynaptic membrane

• With the postsynaptic neuron inhibited it is less likely to fire action potential

GABA-ergic synapses use [blank as a neurotransmitter

g-aminobutyric acid (GABA)

What releases GABA into the synaptic cleft

An Action potential triggers the release

What does the adrenergic synapse use

The monoamine neurotransmitter norepinephrine (NE)

What is NE also called

Noradernaline

Monoamines and neuropeptides bind to what on the postsynaptic membrane

G-protein coupled receptors

What do the G-protein coupled receptors do

Activate second-messenger systems such as cyclic AMP (cAMP)

What is a difference of Adrenergic synapses compared to cholinergic and GABA-ergic synapses

They are slower to respond

They have the advantage of enzyme amplification

• A single molecule of NE produced vast numbers of product molecules in the cell

How long does neurotransmitter stay bound to a receptor for

1 ms

What happens if the presynaptic cell continues to release neurotransmitter

One molecule is quickly replaced by another and the postsynaptic cell continues to be stimulated

How to end a neuron signal

The presynaptic cell stops releasing neurotransmitter

The neurotransmitter that is already in the synapse is cleared

What are the three ways clearance of neurotransmitter can occur

Degradation, Reuptake, Diffusion

Degradation

Enzyme in synaptic cleft breaks down neurotransmitter

What is an example of degradation

Acetylcholinesterase (AChE) breaks ACh down into choline and acetate

Reuptake

Neurotransmitter (or its breakdown products) are reabsorbed into the axon terminal

Example of reuptake

Chonine from ACh is recycled to make new ACh

Difussion

Neurotransmitter (or its breakdown products) simply diffuese away from the synapse into the nearby ECF

Neuromodulators

Chemicals secreted by neurons that have long term modulatory effects on groups of neurons

What can neuromodulators do

• May alter the rate of neurotransmitter synthesis, release, reuptake, or breakdown

• May adjust sensitivity of postsynaptic membrane

What is an example of a simple neuromodulators

Nitric Oxide (NO)

• Gas that enters postsynaptic cells and activates second messenger pathways (for example, relaxing smooth muscle)

Neuropeptides are chains of amino acids that can act as

Neuromodulators

• Enkephalins and endorphins are neuropeptides that inhibit pain signals in the CNS

Neural integration

The ability to process, store, and recall information and use it to make decisions

Chemical synapses allow for what

Decision-making

• Brain cells are incredibly well connected, allowing for complex integration

• Pyramidal cells of cerebral cortex have about 40,000 contacts with other neurons

What is a trade off of chemical transmission

It involves a synaptic delay that makes information travel slower than it would if there was no synapse

What is phase 1 of the excitation of muscle fibers

1. Action potential arrives at axon terminal at neuromuscular junction

2. ACh is released; it binds to the receptors on the sarcolemma

3. The ion permeability of the sarcolemma changes

4. Local change in membrane voltage (depolarization occurs)

5. Local depolarization (end plate potential) ignites AP in sarcolemma

What are examples of different neurotransmitters causing different types of postsynaptic potentials

Glutamate and aspartate produce EPSPs in brain cells

Glycine and GABA produce IPSPs

Why might a neurotransmitter excite some cells and inhibit others

It depends on the ligand receptors in the postsynaptic membrane

What are two neurotransmitters that excite some cells and inhibit others

ACh and NE

What type of muscle does ACh excite and what type of muscle does it inhibit

Skeletal; Cardiac

Summation

The process of adding up postsynaptic potentials and responding to their net effect

What does a neurons response depend on

Whether the net input is excitatory or inhibitory and if it goes above the minimal threshold of -55mvp

Where does summation occur

In the trigger zone (Axon hillock)

Temporal summation

When a single synapse generates EPSPs so quicly that each is generated before the previous one

What does temporal summation allow

EPSPs to add up over time to a threshold voltage that triggers an action potential

Spatial summation

When EPSPs from several different synapses add up to the threshold value at an axon hillock.

The simultaneous input from multiple presynaptic neurons is required for the postsynaptic neuron to fire

Facilitation

A process in which one neuron enhances the effect of another

When does presynaptic facilitation ocuur

When one presynaptic neuron enhances another one which increases the necessary synaptic transmission

Example of presynaptic facilitation

Facilitating neuron releases serotonin which makes voltage gated calcium channels in the axon terminal stay open longer

When does presynaptic inhibition occur

When one presynaptic neuron suppresses another one which reduces or halts unwanted synaptic transmission

What is an example of presynaptic inhibition

Inhibition neuron releases GABA which prevents voltage-gate calcium channels in axon terminal from opening and so little or no neurotransmitter is released

What must happen for skeletal muscle to contract

Activation at a neuromuscular junction

• Must receive nervous system stimulation

• Action potential must be generated in the sarcolemma

Excitation-contraction coupling

• Action potential propagates along sarcolemma

• Intracellular calcium levels must ris

1st step of excitation of a muscle fiber

Arrival of nerve signal

2nd step of excitation of a muscle fiber

ACh is released

3rd step of excitation of a muscle fiber

ACh binds to a receptor

4th step of excitation of a muscle fiber

The opening of a ligand regulated ion channel and the creation of end-plate potential

5th step of excitation of a muscle fiber

Opening of voltage-regulated ion gates; creation of action potentials