Bio 2201- Action potential, neurotransmitters, diseases

What is action potential

a neural impulse; a brief electrical charge that travels down an axon - an electrochemical message sent along the neuron (A wave of depolarization)

What is polarization?

A positive electrical charge outside of the cell, and a negative electrical charge inside of the cell simultaneously

What is depolarization?

When a cell undergoes a shift in electrical charge (After threshold has been met), resulting in less negative charge inside of the cell

What is the all or none principal

A stimulus triggers and action potential or it doesn't. An impulse is either strong enough to send a message to promote an action, or to weak; resulting in no action

What is the wave of depolarization?

Primarily the movement of two positive ions (Na, And K) from one side of the axon cells membrane, to the other; there are three phases

What occurs during resting phase?

The neuron is capable of being stimulated whenever the excitatory stimulus is strong enough

- Uneven distribution of + charged ions outside the membrane, and - charged ions inside the membrane

- The difference in charge is usually around -70mV

- 3 Na+ are leaving, while 2k+ are entering; this is done via a sodium-potassium pump - maintaining the difference in charge

- The difference in charge is called the ELECTROCHEMICAL GRADIENT - however our bodies always want homeostasis, so it will try and fix the imbalance

What is the electrochemical gradient

It is the diffusion gradient of an ion, which is affected by both the concentration difference of an ion across a membrane (a chemical force) and the ion's tendency to move relative to the membrane potential (an electrical force).

What are the 3 types of ion channels

voltage gated, ligand gated, mechanically gated

What is a voltage gated ion channel

a channel that opens or closes in response to a shift in charge, or changes in membrane potential

EX: Sodium channels open at around -55mV, or when threshold is met

What is a ligand gated channel

Opens only when a special chemical, such as a neurotransmitter, binds to it

EX: Serotonin

What is a Mechanically gated channel

Type of ion channel that opens and closes in response to physical stretching of the membrane

EX: Na/k pump

What occurs during depolarization?

- Environmental stimulus occurs (-55mV)

- K+ gates close - Na+ gates open

- Na+ ions rush into the axon, neutralizing the negative charge, this change in charge is called the action potential

- (The axon had become massively depolarized (40mV)) due to the introduction of the electrical current

What does the depolarization cause

causes a biological chain of reaction causing gates of neighbouring voltage-gated Na+ channels to open - this continues as the impulse travels along the axon

- Impulse continues to move along the axon as more Na+ channels are activated in a wave-like fashion until it reaches axon terminals

What occurs during repolarization

Sodium channels close and potassium channels open, restoring the resting potential.

- Voltage gated k+ gates are reopened, letting k+ ions leave the cell in an attempt to rebalance charged

- Na+ gates are closed (dropping to 75mV)

- Once this voltage is reached all the voltage gates close and the Na/K pumps take over - bringing things back to their resting level

What is hyperpolarization

Hyperpolarization refers to a state where the potential across the membrane is more negative than the resting potential

- also known as the refractory period

- neurons cannot be refired during this time

Inhibitory vs. Excitatory Neurotransmitters

Excitatory promotes the action of a neuron (creates action potential) while Inhibitory discourages the action of a neuron) lowers the action potential

Acetylcholine

- Primary neurotransmitter in the somatic, and parasympathetic nervous system

- Can have excitatory and inhibitory effects

- excitatory in skeletal muscles - inhibitory in cardiac muscles

- Influences heart rate + digestion

Dopamine

EXCITATORY

- Controls skeletal muscles

- Elevates mood - associated with reward, pleasure and motivation - attention and movement

Seretonin

INHIBITORY

- Involved in alertness, sleepiness, thermoregulation, and mood

- Associated with digestion and appetite

GABA (gamma-aminobutyric acid)

INHIBITORY

- Most common inhibitory neurotransmitter of the brain

- helps calm neuro activity, reduces anxiety, and promotes relaxation

Glutamate

EXCITATORY

- Neurotransmitter of the cerebral cortex, accounts for 75% of all excitatory transmissions in the brain

- Involved in learning, memory, and cognition

Norepinephrine (No-adrenaline)

EXCITATORY

- Primary neurotransmitter in the sympathetic NS

- Plays a role in the bodies fight or flight response

- Associated with alertness, stress response, and focus

What are the 5 main disorders of the nervous system

1. Multiple sclerosis

2. Alzheimers disease

3. Parkinsons disease

4. Meningitis

5. Huntingtons disease

What does valium do

Increases release of GABA:

- Given to people with intense social anxiety, helps calm people down

What does prozac do

Increases release of serotonin:

- Antidepressant - given to people with a chemical imbalance of the brain, who do not produce enough serotonin

Symptoms of Multiple Sclerosis

visual disturbances, weakness, loss of muscular control, speech disturbances - Relapses of symptoms followed by periods of time without symptoms

- Tremor, Restricted movement, loss of control of movement of balance, Muscle spasms, Numbness or abnormal sensation

Causes of Multiple Sclerosis

not exactly known; autoimmune response; researching viruses, genetics, environment

How does Ms Work

Myelin sheath becomes damaged due to immune system attacking the myelin

- B cells (type of white blood cell that makes infection-fighting proteins called antibodies) enter cns from the bloodstream after wall that prevents b cells from entering brain is broken

- Once inside the Cns, B cells attack myelin sheath instead of defend it

- B and T cells send signals called cytokines (Other types of infectious defenders) to fight, which causes inflammation

- inflamed areas of Cns can become scared when body tries to fix the problem

Treatment for Ms

- Scientists can target specific B cells that trigger the attack on myelin by creating anti - body medicines that target CD20 protein, but not other proteins - successfully slowing down disease

- Steroids (limit the immune system)

- No real "Cure"

Symptoms of Alzheimers

(Caused by irregularities in brain structure)

- Difficulty Sleeping

- Disturbed memory

- Drastic mood changes + increasing confusion

- Short term memory loss

- Paranoia and hallucinations

Causes of Alzheimers

abnormal build-up of proteins in and around brain cells

- Irregularities in brain structure/ tissue in the form of misfoled proteins called plaques and neurofibrillary fibres

What happens during the progression of Alzheimers

- Plaques arise when another in the fatty membrane surrounding nerve cells get sliced up by a particular enzyme

- Resulting in beta amyloid proteins which are sticky and clump together

- Beta amyloid clumping causes plaques - these clumps block signalling and communication between cells, and trigger immune reactions that cause the destruction of disabled nerve cells

- Neurofibrillary tangles are built from a protein called tau

- Tangles make tubes for nutrients to get ti nerve cells - Alzheimers cause tau to collapse into twisted strands/tangles causing the tubes to disintegrate and cut off/ obstruct supply of nutrients from the nerve cell - causing cell death

What are the steps of alzheimers?

1. Short term memory loss due to destructive pairing of plaques and tangles in hipocamus - proteins then invade other parts of the brain

2. Proteins start to destroy ability to process logical thoughts

3. Proteins destroy region involved with emotions, causing erratic mood changes

4. Proteins destroy top of brain, causing paranoia and hallucinations

5. Once proteins reach rear of brain, plaques and tangles work together to erase the minds deepest memories

6. Control centre involved with heart rate + breathing is overpowered, resulting in death

Treatment for alzheimers

- Slowing procedure - helps reduce the break down of acetylcholine, a chemical messenger in the brain which is decreased in Alzheimers patients due to death of nerve cells which produce it

- Plaque Vaccine - Helps train bodies immune system to attack beta - amyloid plaque before they form clumps

Symptoms of parkinsons

Most visible features: Slowness, Tremors, And muscle rigidy

Non motor symptoms: depression, loss of smell, cardiovascular problems, bladder dysfunction

Causes of Parkinsons

associated with degradation of substantia nigra

What occurs during the progression of parkinsons

Focuses on neurons in brain regions associated with overt motor symptoms: Region of midbrain called Substantia nigra which is critical for facilitating movement

- Domaminergic neurons in substantia nigra die, causing malfunction + motor problems

- Caused by clumps of misfolded proteins in neurons called Lewy Bodies: Misfoled protein called alpha synuclein is found within lewy bodies and form repeated units called oligomers, or fibres - these are toxic to neurons and drive parkinsons

- Alpha synuclein overwhelms the unwanted protein degrading machinery found in the neuron - key factor in what kills neurons

- Another potential cause is when the mitochondria cannot break apart or struggles to meet the cell's needs. This means that the cells are unable to perform proper neuronal function.

-Another potential cause is cells surrounding the neurons called glia and more specifically microglia, is thought to take up cellular debris of neurons responsible for dopamine, which triggers immune responses in the form of cytokines, which can damage surrounding neurons.

Treatment of Parkinson's

- Dopamine replacement drugs are used to replace deficit of Dopaminergic neurons in substantia nigra

- Enhancing the clearance of abnormal proteins and blocking their transmission

- Improving function of mitochondria

- targeting Neuroinflamation

causes of meningitis

Infection (virus, bacterial, fungal)

Symptoms of meningitis

headache, fever, stiff neck, High temperature, Vomiting, Cold hands/feet, Breathing quickly, Muscle/ joint pain, Pale or blotchy skin, Hearing loss + light sensitivity, Confusion occurs as pressure on the brain increases due to inflammation

What occurs during the progression of meningitis

- Bacterial meningitis: contracted by breathing in particles of bacteria from mucus and saliva after an infected person coughs/sneezes

- Bacteria enter the body via the nose, mouth, and/or throat

- Once inside, bacteria gain rapid access to surrounding tissue entering the surrounding membranes and the bloodstream

- Once in the bloodstream, bacteria trick the brain blood barrier into letting them through, and infect the meninges once inside the brain - which triggers inflammation as our body's immune response kicks in, causing headaches and fever

p Rapidly multiplying bacteria release toxins a few hours into the infection process; causing blood vessels to break down and blood to seep out

- Toxins burn through 02 in the blood, reducing the amount that gets to the lungs and kidneys - increasing the chance of organ shutdown

Treatment for meningitis

- Steroid medication to help swelling around the brain

- Oxygen is provided through a face mask ( if there is any trouble breathing )

- Antibiotics are given directly into the vein

- Vaccines are given to people with weak immune systems, or children - also people who work in large group settings where an outbreak would be fatal

- Corticosteroids may be given to reduce inflammation and swelling in the brain

Causes of Huntington's Disease

Inherited defect in a single gene

What occurs during the progression of huntingtons disease

- Inherited disease causes by a mutation of the Huntington Gene

- Too many repeats in sequence where bases spell CAG

- Mutated Huntington proteins are broken down to shorter fragments by caspases and other proteases. The fragments cause toxicity.

- Aggregates may be responsible for the toxic effects of mutated Huntington

Symptoms of huntingtons

- Symptoms develop in adulthood

- Changes in movement, cognition, and behaviour (dementia, clumsiness)

Treatment for huntingtons

- No cure, but treatments reduce the symptoms

- Therapies help people with Huntington's disease work on movement and speech