Task 1

Task 1

·         Researchers at the University of Pennsylvania School of Medicine have discovered the mechanism that facilitates how two ion channels collaborate in the control of electrical signals in the brain ·         The channels were anchored by a third protein at key locations on the nerve cell surface, allowing them to work together to set the timing and pattern of nerve impulses. ·         this channel partnership mechanism is present in all vertebrates, but is lacking in invertebrates ·         The elucidation should aid effort  to develop new treatment for epileptic seizures, pain, and abnormal muscle movements. ·         Electrical impulses in neurons are created when these ions are allowed to return to their original locations by passing rapidly through channels in nerve cells' outer membranes.

·         They are two ion channel collaborate in the control of electrical signal in the brain. ·         There are protein channel and carrier protein. ·         Vertebrate have both CNS and spinal cord but in invertebrate only PNS present. ·

·         What are two channel involved? ·         What is the third protein and how it works together and set the timing and pattern of nerve impuls? ·         How nervous system functions in invertebrate without CNS? ·         How can we explain two ion channels collaborate in the control of electrical signals in the brain? ·         What is the relationship between potassium and sodium channels in neurotrans-mission?

·         Refer to lecture notes ·         Reference book ·         Search internets

1. what are two channels involved

         Potassium channel and sodium channel, cells pump extra potassium into their interiors, and pump extra sodium out to the surrounding fluid. Electrical impulses in neurons are created when these ions are allowed to return to their original locations by passing rapidly through channels in nerve cells' outer membranes. Nerve cells possess wire-like extensions, called axons, which initiate these impulses and carry them from one cell to the next.

2. What is the third protein and how it works together and set the timing and pattern of nerve impulse?

            The third protein is ankyrin-G because in a study by Penn's Edward Cooper, MD, PhD, Assistant Professor of Neurology, and colleagues, and the research team was able to identify a molecular motif that allows both channel types to link to a protein called ankyrin-G. The function of Ankyrin-G, in turn, it binds tightly to the nerve cell's cytoskeleton, ensuring the channels' stabilization at the initial segment. The chemical motif identified in the potassium channels was nearly identical to that previously discovered in sodium channels, revealing that the potassium and sodium channels link to the ankyrin-G protein in a similar manner.

            "The ankyrin-G-interaction with potassium and sodium channels establishes a unique domain of the cell for initiating the nerve impulse and for boosting the impulse across the nodes of Ranvier," states Cooper.

            Sodium and potassium are salt molecules (or ions) found throughout the body. Cells pump extra potassium into their interiors, and pump extra sodium out to the surrounding fluid. Electrical impulses in neurons are created when these ions are allowed to return to their original locations by passing rapidly through channels in nerve cells' outer membranes. Nerve cells possess wire-like extensions, called axons, which initiate these impulses and carry them from one cell to the next.

            The efficient and speedy passage of nerve impulses along axons is aided by the presence of an insulating cover, known as myelin, which maintains the electrical activity along the entire length of the axon. The nerve impulse is able to skip across the unmyelinated regions of the axon at the nodes of Ranvier, with the help of sodium and potassium channels.

            Cooper had explain that Myelination and the coupling of axonal sodium and potassium channels are fundamental improvements in the nervous system, and these changes are probably necessary for the vertebrate 'life-style'. He also said that people can only be large and fast-moving if you have a nerve impulse mechanism that is both rapid and highly reliable.

3.  How nervous system functions in invertebrate without CNS?

Invertebrates is an animal which do not have a backbone. The spinal cord and brain make up the CNS. Cnidarians, Nematoda, Annelida,

However, nervous system do evolve from sponges to higher invertebrates which are annelids, arthropods and some mollusks

Sponges are the only animals without neurons

In Cnidarians (sea anemones, corals, jellyfish, freshwater Hydra), there is a simplest existing nervous system which is known as nerve net. Nerve net extends throughout the body and controls simple movements of the body wall and tentacles. E.g: In jellies the net primarily commands the body wall to slowly contract and expand for swimming and the tentacles to move through the water

In a swimming cnidarians or medusae, their radial symmetry is often associated with a nerve ring and some of these animal have certain neurons condensed into simple ganglia/ ganglion.

The beginnings of a true CNS is only find when we progress from cnidarians to bilaterally symmetric animals such as platyhelminthes (flatworms, tapeworms and so on)

Complex ganglionic nervous system are characteristic of higher invertebrates which include annelids, arthropods and some mollusks

4. How can we explain two ion channels collaborate in the control of electrical signals in the brain?

An action potential are generated by a special types of voltage- activated ion channels, which is embedded in cell’s plasma membrane. There are two types of voltage- activated ion channels which are voltage- gated Na+ and voltage- gated K+.

The voltage- gated Na+ channel has two gates: an activation gate and inactivation gate. The voltage- gated K+ channel only has one gate, which can be either open or closed.

Both K+ and Na+ channels are closed. When Na+ channel open, Na+ rush into the cell. Interior of the cell become more positive. Hence, an action potential is generated. This is known as depolarizing phase. In repolarizing phase, Na+ channel closed, K+ channel open. K+ leave the cell and inside the cell become more negative. At undershoot/ hyperpolarization, Na= channel closed but K+ channel remain open because of their slow moving gate, K+ keep flowing out of the cell.

5. What is the relationship between potassium and sodium channels in neurotrans-mission?

1	The inside of the cell is slightly negatively charged (resting membrane potential of -70 to -80 mV).
2	A disturbance (mechanical, electrical, or sometimes chemical) causes a few sodium channels in a small portion of the membrane to open.
3	Sodium ions enter the cell through the open sodium channels. The positive charge that they carry makes the inside of the cell slightly less negative (depolarizes the cell).
4	When the depolarization reaches a certain threshold value, many more sodium channels in that area open. More sodium flows in and triggers an action potential. The inflow of sodium ions reverses the membrane potential in that area (making it positive inside and negative outside the electrical potential goes to about +40 mV inside)
5	When the electrical potential reaches +40 mV inside (about 1 millisecond later), the sodium channels shut down and let no more sodium ions inside (sodium inactivation).
6	The developing positive membrane potential causes potassium channels to open.
7	Potassium ions leave the cell through the open potassium channels. The outward movement of positive potassium ions makes the inside of the membrane more negative and returns the membrane toward the resting membrane potential (repolarizes the cell).
8	When the membrane potential returns to the resting value, the potassium channels shut down and potassium ions can no longer leave the cell.
9	The membrane potential slightly overshoots the resting potential, which is corrected by the sodium-potassium pump, which restores the normal ion balance across the membrane and returns the membrane potential to its resting level.
10	The membrane potential slightly overshoots the resting potential, which is corrected by the sodium-potassium pump, which restores the normal ion balance across the membrane and returns the membrane potential to its resting level.
11	Now, this sequence of events occurs in a local area of the membrane. But these changes get passed on to the next area of membrane, then to the next area, and so on down the entire length of the axon. Thus, the action potential (nerve impulse or nerve signal) gets transmitted (propagated) down the nerve cell.­

Task 3

Task 3

Fact	Idea	Learning issue	Actions plan
1. Ravi is good in academic and co-curriculum 2. He is a very talkative person, and always been chosen in school debate and forum 3. He is the best student in his batch and at the same time, he is also a leader for his school football team 4. He involved in a road accident with a severe head injured. 5. He was coma in hospital for one week 6. Mother worries whether the accident will affect his ability to speak and hear 7. His football coach and teammates worried about his performance in the coming football match. 8. Teacher concerned about his performance in academic.	1. People in coma can hear but cannot respond to stimulation. 2. A coma is a deep state of unconsciousness, which an individual is not able to react to his or her environment. 2. Ravi had severe head injured so, his neuron had damage. 3. The neuron damage can prevent the transmission of impulse that made the person coma. 4.	1. How coma occur? 2. What causes in head injured people? 3. What is the effect of Ravi after awake. 4. What is the justification about his condition that occur in his central nervous system. 5. Is recovery from coma is possible?	1. Refer reference books 2. Search in the internet 3. Discuss with other group members

1. How coma occur?

Coma is commonly a result of trauma, bleeding and/or swelling affecting the brain. Inadequate oxygen or blood sugar (glucose) and various poisons can also directly injure the brain to cause coma.

2. What is the effect of Ravi after awake.

a) Will the head injury cause permanent brain damage?

This depends on how bad the injury was and how much damage it did. Most head injuries don't cause permanent damage.

b) What about memory loss?

It's common for someone who's had a head injury to forget the events right before, during and right after the accident. Memory of these events may never come back. Following recovery, the ability to learn and remember new things almost always returns.

c) What happen after coma?

When coming out of a coma, a person will often be confused and can only slowly respond to what's going on. It will take time for the person to start feeling better. Whether someone fully returns to normal after being in a coma depends on what caused the coma and how badly the brain may have been hurt. Sometimes people who come out of comas are just as they were before they can remember what happened to them before the coma and can do everything they used to do. Other people may need therapy to relearn basic things like tying their shoes, eating with a fork or spoon, or learning to walk all over again. They may also have problems with speaking or remembering things. Over time and with the help of therapists, however, many people who have been in a coma can make a lot of progress. They may not be exactly like they were before the coma, but they can do a lot of things and enjoy life with their family and friends.

5. Is recovery from coma is possible?

Outcomes of coma are from recovery to death. Comas normally last a few days to a few weeks. But in some case it may lasted as long as several year. The time taken is depending on the severity of injury and also depends on disease. There are there possibilities that may occur after the coma, first the patients may come out from coma, second some may progress to vegetative state, and third, some may die. Some patients who have entered a vegetative state go on to regain a degree of awareness. Others remain in a vegetative state for years or even decades (the longest recorded period being 37 years).

The vegetative state is in which the patients in persistent vegetative state have lost all cognitive neurological function but are still able to breathe and may exhibit various spontaneous movements. They may even be awake and appear to be normal but, because the cognitive part of their brain no longer functions, they are not able to respond to their environment. A vegetative state can last for years.

            The outcome for coma and vegetative state depends on the cause, location, severity and extent of neurological damage. A deeper coma alone does not necessarily mean a slimmer chance of recovery, because some people in deep coma recover well while others in a so-called milder coma sometimes fail to improve.

Many people recover their full physical and mental functioning when they emerge from a coma. Others require various forms of therapy to recover as much functioning as possible. Some patients never recover anything but very basic body functions.  

People may emerge from a coma with a combination of physical, intellectual and psychological difficulties that need special attention. Recovery usually occurs gradually patients acquire more and more ability to respond. Some patients never progress beyond very basic responses, but many recover full awareness. Regaining consciousness is not instant: in the first days, patients are only awake for a few minutes, and duration of time awake gradually increases. The coma patient awakes sometimes in a profound state of confusion, not knowing how they got there and sometimes suffering from dysarthria, the inability to articulate any speech, and with many other disabilities.

Predicted chances of recovery are variable owing to different techniques used to measure the extent of neurological damage. All the predictions are based on statistical rates with some level of chance for recovery present: a person with a low chance of recovery may still awaken. Time is the best general predictor of a chance of recovery: after 4 months of coma caused by brain damage, the chance of partial recovery is less than 15%, and the chance of full recovery is very low.

The most common cause of death for a person in a vegetative state is secondary infection such as pneumonia which can occur in patients who lie still for extended periods.

Task 2

Task 2

Fact	Idea	Learning issue	Action plan
Illness - Types of medicine - Duration recover Headache - Panadol activefast - 30 minutes Headache - Ponstan (200 mg) - 15 minutes Sedative - Diazepam (1 mg) - 2 minute Sedative - Propofol - 5 minute Back pain - Voltaren SR 100 - 15 minutes Back pain - Ponston (200 mg) - 15 minutes	1. As we know, sedative is one type of medicine. 2. Diazepam is one type of sedative.	1. What is sedative? 2. What is the content of Panadol activefast, Postan, Diazepam, Propofol, Voltaren SR 100,Poston? 3. Why Diazepam work fastest than other type of medicine? 4. Why does sedative types of medicine have shorter duration compared to others type of medicine? 5. How would medicine affect the function of neurotransmitter?	1. Refer reference books 2. Search in the internet 3. Discuss with other group members

1. What is sedative?

- An agent or drug that sedates; Calming, soothing, inducing sleep, tranquilizing
en.wiktionary.org/wiki/sedative. A sedative  is a substance that induces sedation by reducing irritability or excitement ( from Wikipedia).

- Sedatives are drugs that decrease activity and have a calming, relaxing effect. People use these drugs mainly to reduce anxiety. At higherdoses, sedatives usually cause sleep. 

2. What is the content of Panadol activefast, Postan, Diazepam, Propofol, Voltaren SR 100,Poston?

Type of medicine	Ingredient
Panadol activefast	Active ingredients - paracetamol 500mg per tablet. (plus sodium 173mg, and potassium sorbate E202)
Postan	Ponstan Forte tablets contain the active ingredient mefenamic acid, which is a type of medicine called a non-steroidal anti-inflammatory drug (NSAID). NSAIDs are used to relieve pain and inflammation
Diazepam	ingredient of diazepam rectal gel, is a benzodiazepine anticonvulsant with the chemical name 7-chloro-1,3-dihydro-1 -methyl-5-phenyl-2H-1,4-benzodiazepin-2-one.
Propofol	The active ingredient is 2,6-di-isopropylphenol.
Voltaren SR 100,	hydroxypropyl methylcellulose, iron oxide, lactose, magnesium stearate, methacrylic acid copolymer, microcrystalline cellulose, polyethylene glycol, povidone, propylene glycol, sodium hydroxide, sodium starch glycolate, talc, titanium dioxide.

3. Why Diazepam work fastest than other type of medicine?

Diazepam is a type of benzodiazepines and a type of tranquilliser, benzodiazepines can make you less worried and more relaxed. They can also help some patients sleep better. They work faster than other treatments for anxiety, but they can have serious side effects. You may feel sleepy or doped up. You may have trouble remembering things or concentrating, benzodiazepines can make you feel better quickly. Benzodiazepines generally work faster than other drug treatments for anxiety disorder, usually within a week. How it’s work? Benzodiazepines change the way a chemical called gamma-aminobutyric acid (GABA) works in your brain. GABA stops some cells in your brain communicating with each other, slowing down your brain. Benzodiazepines help GABA work harder, slowing down your brain even more. As a result, you feel calmer. Benzodiazepines also help you sleep.

4. Why does sedatives types of medicine have shorter duration compared to others type of medicine?

Barbiturates are types of sedatives. Barbiturates are drugs that act as central nervous system depressants, and, by virtue of this, they produce a wide spectrum of effects, from mild sedation to total anesthesia.  Ultrashort-acting barbiturates are commonly used for anesthesia because their extremely short duration of action allows for greater control. These properties allow doctors to rapidly put a patient "under" in emergency surgery situations. Doctors can also bring a patient out of anesthesia just as quickly should complications arise during surgery. The middle two classes of barbiturates are often combined under the title "short/intermediate-acting." These barbiturates are also employed for anesthetic purposes, and are also sometimes prescribed for anxiety or insomnia.

The principal mechanism of action of barbiturates is believed to be their affinity for the GABA_A receptor. GABA is the principal inhibitory neurotransmitter in the mammalian central nervous system (CNS). It plays a role in regulating neuronal excitability throughout the nervous system. Barbiturates bind to the GABA_A receptor at the alpha subunit, which are binding sites distinct from GABA itself and also distinct from the benzodiazepine binding site. Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor.

 In addition to this GABA-ergic effect, barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. Taken together, the findings that barbiturates potentiate inhibitory GABA_A receptors and inhibit excitatory AMPA receptors can explain the CNS-depressant effects of these agents. At higher concentration they inhibit the Ca²⁺-dependent release of neurotransmitters. Barbiturates produce their pharmacological effects by increasing the duration  of chloride ion channel opening at the GABA_A receptor (pharmacodynamics: this increases the efficacy of GABA), whereas benzodiazepines increase the frequency of the chloride ion channel opening at the GABA_A receptor (pharmacodynamics: this increases the potency of GABA). The direct gating or opening of the chloride ion channel is the reason for the increased toxicity of barbiturates compared to benzodiazepines in overdose.^[14][15]

Further, barbiturates are relatively "promiscious" (i.e. non-selective) compounds that bind to an entire superfamily of ligand-gated ion channels, of which the GABA_A receptor channel is only one of several representatives. Surprisingly, while GABA_A receptor currents are increased by barbiturates, ligand-gated ion channels that are predominantly permeable for cationic ions are blocked by these compounds. For example, neuronal nACHR channels are blocked by clinically relevant anaesthetic concentrations of both thiopental and pentobarbital. Such findings implicate (non-GABA-ergic) ligand-gated ion channels,  the neuronal nAChR channel, in mediating some of the (side) effects of barbiturates.

5. How would medicine affect the function of neurotransmitter?

Drugs interfere with neurotransmission. More specifically, drugs of abuse produce feelings of pleasure by altering neurotransmission by neurons in the reward system that release the neurotransmitter dopamine. Thus, drugs of abuse alter the communication between neurons that is mediated by dopamine. Because the synapse is so complex, there is a variety of sites at which drugs may affect synaptic transmission. One way to affect synaptic transmission is to increase the amount of neurotransmitter that is released into the synaptic space. Drugs like alcohol, heroin, and nicotine excite the dopamine-containing neurons in the ventral tegmental area (VTA) so that they produce more action potentials.  As the number of action potentials increases, so does the amount of dopamine released into the synapse. Amphetamines (e.g., methamphetamine, crystal, crank) actually cause the release of dopamine from the vesicles. This is independent of the rate of action potentials and, depending on dose, can cause a relatively quick and prolonged rise of extracellular dopamine levels.

Figure 3.1: Methamphetamine alters dopamine neurotransmission in two ways. Methamphetamine enters the neuron by passing directly through nerve cell membranes. It is carried to the nerve cell terminals by transporter molecules that normally carry dopamine. In the nerve terminal, methamphetamine enters the dopamine causes  the release of neurotransmitter. Methamphetamine also blocks the dopamine transporter from pumping dopamine back into the transmitting neuron. Methamphetamine acts similarly to cocaine in this way.