Nervous system

- Thousands of stimuli constantly bombard an animal, and its survival depends on identifying these stimuli and responding appropriately.

- Stimuli within body include internal signals such as hunger or fluctuation in blood pressure.

- Stimuli from the outside world include changes in temperature, light, odour or movement that may indicate the presence of predator or of prey.

- Mammalian nervous system can be divided into two: central nervous system and peripheral nervous system.

Central nervous system (CNS)

- CNS consists of brain and spinal cord.- Neurons that transmit information to the CNS are called afferent neurons or

sensory neuron.- Afferent neurons generally transmit information to interneurons or association

neurons in CNS.- Integration involves sorting of and interpreting incoming sensory information and

determining the appropriate response.- Neural messages are transmitted from the CNS by efferent neurons or motor

neurons.- Action by effectors is the actual response to the stimulus.

Peripheral nervous system (PNS)

- PNS consists of cranial nerves and spinal nerves.- Cranial nerves connect the brain with locations mostly in organs of the head and

upper body.- Spinal nerves run between the spinal cord and parts of the body below the head.- Efferent branch of the PNS consists of two functional components: motor system

and autonomic nervous system.- Motor system consists of neurons that carry signals to skeletal muscles.

(voluntary)- Autonomic nervous system regulates the internal environment by controlling

smooth and cardiac muscles and the organs of digestive, cardiovascular, excretory and endocrine systems. (involuntary)

- There are two divisions of autonomic nervous systems: sympathetic division and parasympathetic division.

- Activation of sympathetic division corresponds to arousal and energy generation.- Activation of parasympathetic division generally cause opposite response that

promote calming and return to self-maintenance function.

Neuron

- Neuron is the functional unit of the nervous system.- Neurons produce and transmit electrical signals called nerve impulse or action

potential.- The largest portion of the neuron, the cell body, contains the nucleus, the bulk of

the cytoplasm and most of the organelles.- Dendrite s are typically short, highly branched process specialized to receive

stimuli and send signals to the cell body.- Axon conducts nerve impulse away from the cell body to another neuron or to a

muscle or gland.- At its end the axon divides, forming many terminal branches that end in synaptic

terminals.- The synaptic terminals release neurotransmitter, chemicals that transmit signals

from one neuron to another or from a neuron to an effector.- The junction between a synaptic terminal and another neuron is called synapse.- Many axons are surrounded by a series of Schwann cells, glial cells that form an

insulating covering called the myelin sheath.- Myelin is a white, fatty material found in plasma membrane of Schwann cells.- Gaps in myelin sheath, called node of Ranvier, occur between successive myelin

sheath.

Resting potential

1. The membrane potential in a resting neuron or muscle cell is its resting potential (-70mV). The membrane is said to be polarized.

2. The ion channels that establish the membrane potential have selective permeability, meaning that they allow only certain ions K+ to pass.

3. The diffusion of K+ through open potassium channels is critical for formation of the resting potential.

4. In resting potential, the ion channels allow K+ to pass in either direction across the membrane. Because the concentration of K+ is much higher inside, the chemical concentration gradient favours net outflow of K+.

5. Since the potassium channels allow only K+ to pass, Cl- and other anions inside cannot accompany K+ across the membrane.

6. The outflow of K+ leads to an excess of negative charge inside the cell. This buildup of negative charge within the neuron is the source of membrane potential.

7. The excess negative charges inside the cell exert an attractive force that opposes the flow of additional positively charged K+ out of the cell.

8. The separation of charge thus results in an electrical gradient that counterbalances the chemical concentration gradient of K+.

Modeling of the resting potential

1. The net flow of K+ out of a neuron proceeds until the chemical and electrical forces are in balance.

2. To produce a concentration gradient for K+ like of a neuron, (a) is set up.3. The K+ will diffuse down their concentration gradient into outer chamber. But

because the Cl- lacks a means of crossing the membrane, there will be an excess negative charge in the inner chamber.

4. When the model neuron reaches equilibrium, the electrical gradient will exactly balance the chemical gradient.

5. The magnitude of the membrane potential at equilibrium for a particular ion is called ion’s equilibrium potential.

6. The resting potential is somewhat less negative than (a). This difference reflects the small but steady move of Na+ across the few open sodium channels.

7. Because the concentration of Na+ has a direction opposite to that of K+, Na+ diffuse into the cell.

8. If the model (b) is set up such that the only channels are selectively permeable to Na+, the equilibrium potential of Na+ is +62mV.

9. The resting potential is much closer to EK because there are many open channels to potassium but only a small number of open sodium channels.

10. If Na+ is more readily to cross the membrane, the membrane potential will move towards ENa. Action potential is generated.

Action potential

- Whenever there is a stimulus (light or vibration), the voltage-gated sodium channels will open resulting flow of Na+ into the neuron.

- The influx of Na+ will in turn trigger some more voltage-gated sodium channels to open. If the stimulus is strong enough, the depolarization of membrane will reach a particular point, called threshold (-55mV).

- Action potential is initiated and it has a magnitude that is independent of the strength of the triggering stimulus. (all-or-none law)Mechanism of action potential

1. At the resting potential, most voltage-gated potassium and sodium channels are closed.

2. When stimulus depolarizes the membrane, some gated sodium channels open, allowing more Na+ to diffuse into the cell. The Na+ inflow causes further depolarization, which open more gated sodium channels, allowing even more Na+ to diffuse into the cell.

3. Once the threshold is crossed, this positive feedback cycle rapidly brings the membrane potential close to ENa. This stage is the rising phase.

4. However, two events prevent the membrane potential from actually reaching ENa: voltage-gated sodium channels inactivate soon after opening, halting Na+ inflow; and most voltage-gated potassium channels open, causing a rapid outflow of K+. both events quickly bring the membrane potential back towards EK. This stage is called the falling phase.

5. In the final phase, called the undershoot, the membrane’s permeability to K+ is higher than it is at the resting potential. The gated potassium channels eventually close and the membrane potential returns to the resting potential.

Characteristic of nerve impulse

Refractory period

- The sodium channels remain inactivated during the falling phase and the early part of the undershoot.

- As a result, if a second depolarizing stimulus occurs during this period, it will be unable to trigger an action potential.

- The downtime following an action potential when a second action potential cannot be initiated is called the refractory period.

- When axon is in repolarisation state, the axon membrane is in absolute refractory period. Another action potential cannot be initiated no matter how great a stimulus is applied.

- When the Na gated channels are reset, neuron enters a relative refractory period. During this period, the axon can transmit impulse, but the threshold is higher.

All-or-none law

- An action potential is an all-or-none response, because either it occurs or it does not occur.

- Only a stimulus strong enough to depolarize the membrane to its critical threshold level results in transmission of an impulse along a axon.

Conduction speed

- Several factors affect the speed of conduction of action potential.- One is axon diameter: action potential conducts more rapidly in wider axons than

narrow axons because resistance to electrical current flow is inversely proportional to the cross-sectional are of a conductor.

- One is presence of myelin sheath: myelin sheaths are produced by two types of glia --- oligodendrocytes in the CNS and Schwann cells in the PNS.

- The insulation provided by the myelin sheath has the same effect as increasing the axon’s diameter. It causes the depolarization current associated with the action potential to spread farther along the interior axon.

- In a myelinated axon, voltage-gated sodium channels are restricted to gaps in the myelin sheath called node of Ranvier.

- The cellular fluid is in contact with the axon only at this node. As a result, action potentials are not generated in the regions between the nodes.

- Rather, the inward current produced during rising phase of the action potential at a node travel all the way to the next node, where it depolarizes the membrane and regenerates the action potential. This mechanism is called saltatory conduction because the action potential appears to jump along the axon from node to node.

Mechanism of transmission and spread of impulse along axon

1. An action potential functions as a long-distance signal by regenerating itself from the cell body to the synaptic terminals.

2. At the site where an action potential is initiated, Na+ inflow during the rising phase creates an electric current that depolarize the neighbouring region of the axon membrane.

3. The depolarization in the neighbouring region is large enough to reach the threshold, causing the action potential to be reinitiated there.

4. Immediately behind the travelling zone of depolarization due to Na+ inflow is a zone of repolarisation due to K+ outflow.

5. In the repolarised zone, the sodium channels remain inactivated. Consequently, the inward current that depolarizes the axon membrane ahead of the action potential cannot produce another action potential behind it.

6. This prevents action potential from travelling back towards the cell body.

Synapse

- The majority of the synapses are chemical synapses, which involve the release of a chemical neurotransmitter by the presynaptic neuron.

- The cell body and dendrites of one of the postsynaptic neuron may receive inputs from chemical synapse terminals.

- At each terminal, the presynaptic neuron synthesizes the neurotransmitter and packages it in multiple membrane-bounded compartments called synaptic vesicles.

- The action potential depolarizes the plasma membrane of presynaptic terminal, opening voltage-gated calcium ion channels that allow Ca2+ to diffuse in.

- The resulting rise in Ca2+ concentration in the terminal causes some of the synaptic vesicles to fuse with the terminal membrane, releasing the neurotransmitter.

- The neurotransmitter in synaptic cleft bind to binding site of ligand-gated ion channels and trigger the influx of Na+ and thus initiate action potential.

Postsynaptic potentials

- Binding of the neurotransmitter to a particular part of the channel opens the channel and allows specific ions to diffuse across the postsynaptic membrane.

- The result is generally a postsynaptic potential, a change in the membrane potential of the postsynaptic cell.

- Because these depolarizations bring the membrane toward threshold, they are called excitatory postsynaptic potential (EPSP).

- At the other synapses, a different neurotransmitter binds to channels that are selectively permeable for only K+ and Cl-. When those channels open, the postsynaptic membrane hyperpolarizes.

- Hyperpolarisation produced in this manner are called inhibitory postsynaptic potential (IPSP).

Summation of postsynaptic potentials

- Two EPSPs occur at a single synapse in such rapid succession that the postsynaptic neuron’s membrane potential has not returned to the resting potential before the arrival of the second EPSP. When that happens, the neuron EPSPs add together, an effect called temporal summation.

- EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron can also add together, an effect called spatial summation.

- Through spatial and temporal summation, several EPSPs can depolarize the membrane at the axon hillock to the threshold, resulting in initiation of action potential.

- Summation applies as well to IPSP: two or more IPSPs occurring nearly simultaneously or in rapid succession have a larger hyperpolarizing effect than a single IPSP.

- Through summation, an IPSP can also counter the effect of an EPSP.

Neuromuscular junction

- Neuromuscular junction is a synapse found between a motor neurone and skeletal muscle fibers.

- On stimulation, the synaptic knob release acetylcholine which moves across the synaptic cleft and binds to the receptor on the plasma membrane (sarcolemma) of the muscle fiber. This increase the permeability of plasma membrane to sodium ions.

- This depolarizes the postsynaptic muscle cell and triggers an action potential. The action potential passes along the sarcolemma through the transverse tubule system (T tubule) and deep down into the muscle fiber. The action potential results in muscle contraction.

Sarcomere

- Each striated muscle fiber is a long, cylindrical cell with many nuclei.- The plasma membrane, known as the sarcolemma in a muscle fiber, has multiple

inward extensions that form a set of T tubules.- The cytoplasm of a muscle fiber is called sarcoplasm and the endoplasmic

reticulum is called the sarcoplasmic reticulum.- Myofibrils, which are threadlike structures, run lengthwise through the muscle

fiber. They consist of even smaller structures, the myofilaments or simple filaments.

- There are two types of myofilaments: myosin and actin filament.- Myosin filaments are thick, consisting mainly of the protein myosin.- The thin actin filaments consist mostly of the protein action; they also contain the

protein tropomyosin and the troponin complex that regulate the actin filament’s interaction with the myosin filaments.

- Sarcomere is the basic units of muscle contraction.- Sarcomeres are joined at their ends by an interweaving of filaments called the Z

line. M line is the anchorage site for myosin filaments.

- The I band consists of parts of actin filaments of two adjacent sarcomeres. The A band is wide, dark region that includes overlapping myosin and actin filaments.

- Within the A band is a narrow, light area, the H zone, made up exclusively myosin filaments.

Mechanism of muscular contraction based on the sliding filament theory

1. Muscle fiber in relaxed state. Note that I band and H zone are relatively wide.2. Muscle fiber contracting. Actin and myosin filaments slide past one another,

increasing amount of overlap between actin and myosin filaments. Note that I band and H zone decrease in length. Filaments themselves do not become shorter.

3. Contracted muscle fiber. Actin filaments overlap, eliminating H zone. I band also disappear as Z line are pulled close to myosin filaments.

1. Sliding filament model was developed by two British biologists, Hugh Huxley and Andrew Huxley.

2. When a motor neuron transmits a message, it releases the neurotransmitter acetylcholine into the synaptic cleft.

3. Acetylcholine binds with receptors on each muscle fiber, causing depolarization which causes generation of action potential.

4. Action potential travels along the sarcolemma and into the system of T tubule membrane. Depolarization of the T tubule opens calcium channels in the sarcoplasmic reticulum and stored calcium ions are released into the myofibrils.

5. Calcium ions bind to a protein in the troponin complex on the actin filaments, which changes the shape of the troponin.

6. This change results in the troponin pushing the myotroponin away from the active sites on the actiin filaments. These active sites, also called myosin-binding sites, are now exposed.

7. One end of each myosin molecule is folded into two globular structures called myosin heads. The rounded heads of the myosin molecules extend away from the body of the myosin filaments.

8. Each myosin molecules has a long tail that joins other myosin tails to form the body of the thick filaments.

9. ATP is bound to the myosin when the muscle fiber is at rest.10. Myosin is an ATPase that converts the chemical energy of ATP into mechanical

energy of sliding filaments.11. According to the model, ADP and Pi initially remain attached to the myosin head.

The myosin head is in an energized state; it is cocked.12. The myosin head binds to an exposed active site on the actin filaments, forming a

cross bridge linking the myosin and actin filaments.13. The inorganic phosphate and ADP is then released, which triggers a

conformational change in the myosin head. The myosin bends about 45 degrees, in a flexing motion which pulls the actin filament closer to the center of the sarcomere.

14. A new ATP must be bind to the myosin head before the myosin can detach from the actin. Energized again, myosin heads contact a second set of active sites on the actin filaments; this next set is farther down the molecule, closer to the end of the sarcomere.

15. This series of stepping motions pulls the actin filaments toward the center of the sarcomere.

Sequence of events in muscle contraction

1. A motor neuron realeases acetylcholine, which binds with receptors on the muscle fiber, causing depolarization and an action potential.

2. The action potential spreads through T tubule, triggering Ca2+ release fro, the sarcoplasmic reticulum.

3. Troponin that has bound Ca2+ undergoes a conformational change that causes binding sites on the actin filaments to be exposed.

4. ATP (attached to myosin) is split and the energized myosin head is cocked; it binds to the binding site on the actin filaments, forming cross bridge.

5. The release of Pi form the myosin head triggers the power stroke.6. The power stoke occurs as the filaments is pulled toward the center of the

sarcomere and ADP is released.7. The myosin head binds ATP and detaches from the actin. If the concentration of

Ca2+ is high enough, the sequence repeats from step 3.8. When impulses from the motor neurone cease, Ca2+ is pumped back into

sarcoplasmic reticulum by active transport. The myotroponin once again covers the myosin-binding site.

9. Muscle relaxation is restored.

Drug abuse

Cocaine

- Cocaine stimulates release and inhibits reuptake of norepinephrine and dopamine, leading to CNS stimulation followed by depression.

- Cocaine has an effect on mood which induces brief, intense high with euphoria, followed by fatigue and depression.

- Cocaine addiction results in mental impairment, convulsion, hallucinations, unconsciousness and causes death if overdose.

Curare

- Curare mimics the shape of acetylcholine and competes with acetylcholine to bind to the ligand-gated ion channels on the postsynaptic membrane.

- Thus, no action potentials are initiated in the postsynaptic membrane.- The muscles are unable to contract and may lead to paralysis and causes lung

failure if curare is present in the synaptic cleft of intercostal muscle.