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The nervous system - centre for body control and communication network functions of the nervous system: -Detect any changes (stimuli) that occur inside and outside the body -Define the changes -Respond to the defined changes Terms and Definition Stimulus any change in the external or internal environment which provokes a response Receptor specialized cells that detect a stimulus Neuron cells which transmit nerve impulses Effector organ that respond to the stimuli and bring about a response
Nervous system + endocrine system + enzyme system

Maintain a stable internal environment in human

The organization of the nervous system consists of 2 types of cells 1. Neuron - basic functional unit of nervous system - able to generate and transmit nerve impulses 2. Neuroglia -supporting cells

# Neuron (Nerve cell)

Divided into 3 parts: i.Cell body ii.Dendrites iii.Axons i.. Cell body @ sentron @ soma ~ Carries out maintenance activity, i.e., synthesizes materials required by neurons ~ Possesses organelles such as nucleus, mitochondria, ribosomes, golgi apparatus, endoplasmic reticulum, etc. ~ Cytoplasm contains Nissls granules rich in RNA (for protein synthesis) Various shapes, e.g., sphere or pyramid ii. Dendrites ~ Short extensions from the cell body ~ Carry impulse towards the cell body

iii. Axons ~ Long extensions which carry impulses away from the cell body ~ Terminal end branches with swollen endings known as the synaptic knob ~Possess cytoplasm axoplasm surrounded by axomembrane

3 Types of neurons according to function: 1. Sensory neuron (afferent neuron) Long dendrites and short axons Carries impulses from receptor to CNS 2. Interneuron (in CNS) Connects the sensory neuron to the motor neuron

3. Motor neuron (efferent neuron) Short dendrites and long axons Receive nerve impulses from interneuron and transmit to effector, e.g., muscles and glands

# Neuroglia Cell
-Provides structural support and metabolism for neuron E.g., Schwann cells form myelin sheath surrounding the axon (Myelin sheath) - between 2 nodes of Ranvier - increase the speed of impulse transmission (Nodes of Ranvier) small uncovered parts of myelinated axon between the myelin sheaths

3 Types of Neuron According to Structure Depends on the number of extensions leaving the cell body 1. Unipolar Possesses a single extension from the cell body Characteristic of invertebrate nervous systems and sensory neurons 2. Bipolar Possesses 2 extensions: dendrites and axons, e.g., neuron in the retina

Impulse Transmission

1.Along the axon - as an electrical signal

2.Across the synapse as a chemical signal

3. Multi-polar Possesses a few extensions from the cell body, generally in mammalian nervous systems, e.g., pyramid cells, Purkinje cells and motor neuron

Impulse transmission along the axon 1. Resting Potential 2. Action Potential (depolarization and repolarization) How The Resting Potential Is Maintained 3 types of ions play significant roles to determine the resting potential Sodium (Na+) Potassium (K+) Large negatively-charged organic molecules (amino acids and proteins) Involve 2 mechanisms: K+/Na+ pump Non-voltage gated K+/Na+ channel

# Resting Potential
The potential difference which exists across the axon membrane when the neuron is not conducting an impulse or is at rest It is caused by the unequal distribution of charged ions inside and outside the neuron membrane (inside more negatively charged relative to the outside) axon is polarized No stimulation axon at rest axon is polarized Axon is polarized when it is in resting potential Inner membrane vely charged [Na+] low, [K+] high Presence of anion: ClNegatively charged protein and organic phosphate

Outer membrane +vely charged [Na+] high, [K+] low, Cl- also present These differences will cause electrical potential difference across membrane resting potential ( 70mV

The different concentrations of these types of ions are maintained by an interplay of several factors: 1. 2. 3. Diffusion Electrical attractions and repulsions Active transport across the cell membrane 4. Selective permeability of the axon membrane to these three ions.

# Action Potential
An action potential is the change in the potential difference across an axon membrane which occurs during the passage of a nerve impulse Nerve impulse

During the resting potential, Na+/K+ pump actively transports Na+ and K+ across the membrane against their concentration gradients The presence of more non-voltage gated K+ channels compared to those for Na+ more K+ diffuse out than Na+ diffuse in. Always some Na+ leaking in and this is reduced by the Na+/K+ pump 3 Na+ are transported to the outside membrane for every 2 K+ brought into the cytoplasm of the axon. These processes always more K+ inside so the resting potential is maintained almost entirely by this K+ difference. Presence of anions, e.g., proteins in the cell which are too large to diffuse out The Na+/K+ voltage gated channels are both closed The net result outer membrane is +ve compared to inner membrane Resting potential is established

- an information that passes along the axon, changes the potential difference across the membrane and generate an action potential - only can be transmitted as a series of electrical signals when the stimuli > threshold intensity (> - 50 mV).

The action potential has 3 phases (2 - 3 msec) 1. Depolarization 2. Repolarization 3. Hyperpolarization

2. Repolarization Reversal in polarity to +35 mV voltage-gated Na channels close Voltage-gated K channels open K+ diffuse out of the axon The outside of the neuron becomes more positive relative to the inside The axon membrane is repolarized Action potential alters from +35 to 70 mV 3. Hyperpolarization Voltage-gated K channels are slow to close excess K+ leave the axon Inner membrane becomes more ve the voltage falls slightly below -70 mV hyperpolarization Within a few msec, voltage-gated K channels close Resting potential (-70 mV) is reestablished

1. Depolarization (1 msec) Stimulus reaches a resting neuron, Factors Affecting Impulse Transmission some voltage-gated Na channels 1. Diameter of the axon open - the larger the axon diameter the faster + Na diffuse into the axon the speed of impulse transmission The inside of the neuron becomes - the smaller the diameter, the greater more positive relative to the outside the resistance created by the axoplasm The axon membrane is depolarized lower the speed of impulse More gates open more Na+ transmission diffuse into the axon further depolarization 2. Myelinated neurone - an action potential can only be generated When the membrane potential difference reaches a threshold value, at nodes of Ranvier because Na+ and K+ are able to move across the membrane many more gates open rapid + diffusion of Na sudden increase in the membrane potential Hence, action potential jumps from 1 node difference (+35 mV) of Ranvier to another along the axon The action potential stimulates other increases the speed of impulse transmission Na channels down the axon to open, thus causing the impulse to travel down the axon

The difference in potential between the active and resting membrane parts creates a localized electric current (LEC) LEC stimulates the adjacent part (2nd part) of the membrane Na+ flow in, depolarize and generate a second action potential After the action potential, the first part of the membrane is repolarizing as K+ flow out This process is repeated Impulse is propagated as a series of repolarization and depolarization along the axon

Refractory Period Period after an action potential has passed, i.e., period when axon is not able to transmit a new impulse (5 10 msec) 1. Absolute refractory period the axon membrane is unable to respond to another stimulus action potential is not generated 1 msec 2. Relative refractory period Resting potential is gradually restored by the Na+/K+ pump 5 msec All or Nothing Law All action potentials are of the same amplitude, i.e., after threshold is reached, the size of the action potential produced remains constant and is independent of the intensity of the stimulus

Information is transmitted along a neuron as a nerve impulse which consists of a series of action potentials When a neuron is stimulated, Na+ flow into the neuron depolarization of the inner membrane action potential is generated This part of the membrane is more positive relative to the adjacent part (still at resting potential)

Synapse Connection site between 1. neuron-neuron 2. neuron-muscle

Synaptic knob (at the end of axons) contain mitochondria and synaptic vesicles Synaptic vesicles contain neurotransmitter - important in impulse transmission Neurotransmitter - small chemicals found in the synaptic vesicle - helps to transmit an impulse across the synapse Neuron that carries impulse to synapse presynaptic neuron covered by presynaptic membrane. Neuron that carries impulse away from synapse - postsynaptic neuron covered by postsynaptic membrane

-Impulse that reach synaptic knob stimulates opening of Ca channels -Ca2+ (in the interstitial fluid) enter the knob -Stimulate binding of vesicles and presynaptic membrane - Vesicles release neurotransmitter into synaptic cleft (each synaptic vesicle contains 10 thousand molecules of neurotransmitter -Neurotransmitter binds with receptor on postsynaptic membrane -Change configuration of protein on postsynaptic membrane -Na channels open -Na+ enter and depolarize postsynaptic membrane excitatory postsynaptic potential (EPSP) -If EPSP reaches the threshold level, action potential is generated and transmitted to the 2nd neuron/muscle *If acetycholine stays in the receptor sites, Na channels remain open - continually producing action potentials

-To prevent continuous production of action potential remove the neurotransmitter (nt) i. Direct uptake of nt e.g., noradrenaline is transported back into the synaptic knob and inactivated by the enzyme monoamine oxidase ii. Enzymes are released to degrade nt e.g., enzyme acetylcholinesterase splits acetylcholine into acetyl coenzyme A and choline taken up by the presynaptic neurone combined to reform acetylcholine Two main neurotransmitters used in the vertebrate nervous system are 1. Acetylcholine Neurons releasing acetylcholine are called cholinergic neurons. Found in most synapses 2. Nonadrenalin (norepinephrine) Neurone releasing nonadrenalin are called adrenergic neurons. Found specifically in the synapses of the sympathetic nervous system 3. Both nt can be inhibitory or excitatory, depending on the type of receptor 4.Other neurotransmitters: Dopamine, serotonin (brain), glutamate, etc.

Functions of Synapse 1. Transmits information between neurons 2. Transmits nerve impulses in one direction because nt are only released by the presynaptic neuron 3. Filters out low-level stimuli of limited importance 4. Protects the effectors from damage by overstimulation, i.e., by action potentials continually being generated

Drugs Chemical substances that cause changes in the natural chemical environment and functioning of the body Can be ingested, injected, inhaled or put into the body in some other ways Used in medicine to help prevent, diagnose and treat diseasse or injuries Psychoactive drugs (PAD) interfere with the nervous system and cause changes in the mental state and behaviour Overdose of PAD over dependence (addiction) of the drug Affect the nervous system by altering the mechanism of synaptic transmission i. Excitatory psychoactive drugs work in various ways: (a) Mimic a natural neurotransmitter, fitting into the same receptors e.g. nicotine mimics acetylcholine. (b) Interfere with the normal enzyme breakdown of a neurotransmitter. The drug (a)/neurotransmitter (b) stays in the receptors & continues to stimulate the postsynaptic membrane - causes continuous stimulation & contraction of muscles E.g. Organophosphate insecticides. ii. Inhibitory psychoactive drugs work in various ways: (a) They prevent the release of a neurotransmitter E.g. Botulinum is a poisonous toxin produced by the bacterium Clostridium. It will stop respiration muscles contraction & resulted in impossible breathing

(b) They block the action of a neurotransmitter at the receptors on the postsynaptic membrane. E.g. Curare is a natural poison. It blocks the action of acetylcholine at neuromuscular junctions stop muscle contraction.

Skeletal Muscle Structure Skeletal muscle is made up of hundreds of muscle fibres. Each muscle fibre - surrounded by connective tissue endomysium. - long, cylindrical in shape & arranged parallel to each other - consists hundreds of myofibrils - cytoplasm sarcoplasm - contain many mitochondria Myofibrils - thin threads that arranged parallel to one another. - made up of alternating light & dark bands due to overlapping strands of contractile protein (myosin & actin). - each contractile unit sarcomere Sarcomere (myofibril basic unit) i. e. region between one Z line &another Z line Myofibrils consist of: Thick filament are composed of protein - myosin - long tail - globular head site for ATPase enzyme. Thin filament are composed of protein actin - helical backbone consist of 2 strand. - contain 2 other proteins (tropomyosin & troponin). Sarcoplasm of muscle fibre consists of i. longitudinal interconnected tubules between the myofibrils - sarcoplasmic reticulum. ii. Transverse tubules which are invaginations of sarcolemma membrane T tubules. Ends of sarcoplasmic reticulum form vesicles terminal cisternae - involved in the intake & release of Ca2+.

The neuromuscular junction (NMJ) a synapse between a motor neurone & skeletal muscle fibres

Each muscle fibre has a region motor end plate where the axon of the motor neurone divides & forms fine branches ending in synaptic knobs. The NMJ includes the motor end plate & the synaptic knob. -On stimulation, the synaptic knob release Ach which binds to the receptors on the sarcolemma. -This increases the permeability of the sarcolemma to Na+. -This depolarises the postsynaptic muscle fibre & triggers an AP. -The AP passes along the sarcolemma through the T tubules system, deep down into the miofibril & results in muscle contraction.

The Sliding Filament Theory suggested by Huxley & Hanson 1. Muscle at rest Outside of muscle membrane +ve charge. Inside of muscle membrane -ve charge. 2. Muscle stimulation Nerve impulse (action potential) travels along a motor neurone & reaches the neuromuscular junction. Acetylcholine (Ach) is released into the synaptic cleft, diffuses to the sarcolemma & bind with receptor on the sarcolemma. When action potential (AP) reaches it threshold value, an AP is created in the muscle fibre. Ach in the cleft is then hydrolyzed & the products are reabsorbed into the motor neurone. AP travels along the sarcolemma, spreads into the T tubules & stimulates the release of Ca2+ from the cisternae terminal at sarcoplasmic reticulum. Ca2+ diffuse out to the sarcoplasm.

3. Actomyosin-Cross bridges formation Ca2+ bind to troponin & alter its shape. Tropomyosin strand moved to the sides & exposed the binding sites. A molecule of ATP binds to myosin head. ATPase is activated. ATP ADP + Pi + ENERGY

6. Repolarization After contraction, Ca2+ is actively absorbed back into the terminal cysterna. Muscle relaxed.

The energy is transferred to myosin head & changes the myosin from low energy configuration high energy configuration. Myosin heads attach to the actin binding sites - actomyosin-cross bridges. 4. Slides ADP & Pi are released. Myosin head returns to it low-energy configuration. It bends & propels the actin towards the centre of sarcomere. Actin & myosin filaments slides between each other. 5. Breakdown of the Actomyosin-Cross bridges A new ATP molecule binds to each myosin head. Each myosin head detaches from the actin & returns to it low energy configuration. Troponin reverts to its original shape & tropomyosin block the binding site on the actin filaments. Myosin heads are ready to bind to the next binding site on the actin filaments.