These notes are intended to accompany lectures in Human Physiology by Dr. Peter King at Francis Marion University, Florence, SC 29502.

The nervous system is part of the bodies control system along with the endocrine system.
The nervous system generally takes care of short term control of body function including skeletal movement. The endocrine system takes care of longer term control

The nervous system is able to receive stimuli and transmit signals between cells, integrate signal information and stimulate an effector (muscle).
The specialized cells that transmit a nerve impulse are neurons.
A nerve is made up of many neurons.

The nervous system can be divided in a number of ways.
Firstly there is a division between the central nervous system, CNS, (the brain and spinal cord) and the peripheral nervous system, PNS, (cranial and spinal nerves and there branches).

The peripheral nervous system is divided into the sensory (afferent) and motor (efferent) systems (neurons going to effectors).
Motor neurons are divided into somatic (to skeletal muscle) and autonomic systems (to smooth and cardiac muscle).

The nervous system is made up of neurons (nerve cells) that transmit nervous impulses and glial cells (supporting cells).
Glial of the CNS
Astrocytes - provide a cellular connection between the neurons and capillaries, transport nutrients and waste.
Control the chemical environment around the neuron.
Absorb and recycle neurotransmitters.
Not the blood brain barrier.

Oligodendrocytes - processes wrap around neurons and insulate them from stimulation from other neurons.Form myelin sheath around axons.
Microglia - small phagocytic white blood cells that migrate through CNS.
Ependymal cells - line the cavities of the CNS that are filled with cerebrospinal fluid (CFS). Have role in monitoring CSF and producing CSF.

Glial of the PNS
Satellite cells - surround the cell bodies of neurons. Thought to assist the neuron in maintaining homeostasis, e.g. chemical environment.
Schwann cells - wrap around the axon and forms a myelin sheath.
Myelin sheath increases the spread of transmission of a nerve impulse along the axon.

Neurons (and muscles) are different from other cells and are excitable cells. Neurons transmit nerve impulses.
Functionally neurons are divided into sensory neurons, interneurons and motor neurons.
Each have an input zone (dendrites), a transmission zone (axon) an output zone (axon terminal) and a cell body (contains the nucleus).

So how do neurons work?
As mentioned earlier neurons are excitable cells.
Neurons maintain an imbalance in charged particles inside and outside of their cell membrane.
The cell traps large negatively charged organic molecules inside the cell, and actively controls the movement of positive ions to produce an electrical potential across the membrane.

Revision - transport across membranes.
Some molecules like O₂ and CO₂ can simply diffuse through a membrane because they are fat soluble.
Larger molecules and charged particles (ions) cannot diffuse through a cell membane but can be transported passively or actively by carriers (proteins imbedded in the membrane)

Back to how a neuron works.
Neurons maintain an imbalance in charged particles inside and outside of their cell membrane.
The cell traps large negatively charged organic molecules inside the cell, and actively controls the movement of positive ions to produce an electrical potential across the membrane.

Protein pumps in the membrane maintain the potential by pumping out 3 Na⁺ ions in exchange for 2 K⁺ ions.
The outside of the cell is more positive than the inside.
This imbalance is called the resting potential of the cell.
For a somatic motor neuron it is commonly about -70 millivolts, but varies in the range of neurons from about -30 mV to about -100 mV.

At their resting potential, neurons are referred to as polarized, because the inside is negative compared to the outside.
Neurons can be stimulated or excited at their dendrites.
Excitation changes the potential across the cell membrane by opening channels and allowing Na⁺ and K⁺ to diffuse through the membrane.

Allowing Na⁺ and K⁺ diffusion leads to a depolarization of the membrane potential.
Such a depolarization event is localized to the area around the point of excitation. Na⁺/K⁺ pumps soon return the potential back to the original resting potential.
The effect of this local depolarization diminishes with distance away from the site of excitation like a ripple from a pebble dropped in a pool.

What causes a local excitation?
Depending on the nature of the dendrites it can be many different criteria.
Such as:touch, stretch, pressure, heat, a chemical etc.

A nerve impulse is triggered when the membrane potential reaches a critical threshold level at the axon hillock.
This is usually attained by the summation of many local depolarization events.
A nerve impulse or action potential travels down the axon away from the axon hillock but does not diminish with distance.

Action potentials are either on or off.

The threshold is the level of depolarization that will cause special ion channels to open that allow diffusion of Na⁺ and K⁺.
These channels are called voltage gated channels.
An action potential results in the axon.

Voltage gated ion channels are located all along the axon.
Opening one voltage gated channel causes a local change in potential that opens adjacent voltage gated channels - these then cause a local change in potential that open adjacent voltage gated channels - these then cause a local change in potential that open adjacent voltage gated channels

- these then cause a local change in potential that open adjacent voltage gated channels
- these then cause a local change in potential that open adjacent voltage gated channels
- these then cause a local change in potential that open adjacent voltage gated channels
- these then cause a local change in potential that open adjacent voltage gated channels
- these then cause a local change in potential that open adjacent voltage gated channels

There are separate voltage gated channels for sodium and potassium.
These channels open at a threshold value and then closed by another 'gate'.
There is a refractory period of about 4 milliseconds where a channel that has closed cannot be reopened. This prevents an action potential going backwards.

Why don't the Na⁺ and K⁺ cancel each other out immediately?
1. There is an electrical gradient that increases the diffusion of Na⁺ into the cell.
2. The concentration gradient is greater for Na⁺ than for K⁺.
3. The Na⁺ channels open first and then close quickly. i.e. large influx of Na⁺ to depolarize area.
4. K⁺ channels are slower to open and stay open longer, K⁺ flows out and membrane area is repolarized (Na⁺ / K⁺ pumps also).

Myelinated axons transmit action potentials (APs) faster.
Voltage gated channels are located at spaces between Schwann cells (nodes of Ranvier).
AP skips from node to node and travels.
Remember : once started an action potential travels the length of the axon. It either happens or doesn't - on or off.

What happens when the AP reaches the axon endings?
The axon end are called terminal boutons or presynaptic endings.
A synapse is the communication area of a neuron and another cell.
As the AP gets to the presynaptic end another type of voltage gated channel is opened - a voltage gated Ca²⁺ channel.
Here Ca²⁺ acts like a second messenger, activates calmodulin ,which activates protein kinase

The end result of the influx of calcium is exocytosis of neurotransmitter stored in vesicles.
The result of an action potenial is the release of neurotransmitter into the synaptic cleft.

Neuron to neuron junction (chemical synapse)
There are many different neurotransmitters.
One common neurotransmitter in the CNS and the PNS is acetylcholine, ACh.
When ACh is released it enters the interstitial fluid and crosses the synaptic cleft.
The post synaptic cell has receptors for ACh.
The binding of the neurotransmitter to its receptor opens ion channels (chemically gated channels).

Opening ion channels will cause a localized change in polarity in the dendrite of the postsynaptic neuron.
Nicotinic receptors (named this because they are also activated by nicotine) open sodium channels and thereby cause an influx of Na⁺ and a local depolarization.
This is called an Excitatory Post Synaptic Potential, or EPSP.

If the postsynaptic cell has muscarinic ACh receptors, binding of ACh opens K⁺ channels.
This causes an outflow of K⁺ and a hyperpolarization.
This is an Inhibitory Post Synaptic Potential or IPSP.

Neurons that use ACh as a neurotransmitter are referred to as cholinergic neurons.

ACh dissociates quickly from its receptor but will bind again if it remains in the cleft.
An enzyme acetylcholinesterase AChE located on the post synaptic membrane, or closely associated to it, breaks down ACh.
Remnants of ACh are reabsorbed by the presynaptic neuron and reformed into ACh in vesicles.

Another common neurotransmitter in the CNS and PNS is norepinephrine (NE).
Its release is triggered in exactly the same way i.e. an AP opens Ca²⁺ channels and vesicles expell their contents by exocytosis.
NE binds to receptors on the post synaptic cell and a second messenger is activated inside the cell and ion channels are opened.
Depending on the receptor an EPSP or a IPSP is produced.

Enzymes, monamine oxidase (MOA) and catechol-O-methyltransferase (COMT) degrade the neurotransmitter.
Norepinephrine is in a group of neurotransmitters called monamines and includes dopamine and serotonin.

Motor neurons
Acetylcholine, ACh, is the neurotransmitter used in all vertebrate neuromuscular junctions in the somatic (voluntary) nervous system.
In the autonomic system there are preganglionic and post ganglionic neurons.

Preganglionic neurons in the autonomic nervous system all use ACh as their neurotransmitter.
Parasympathetic post-ganglionic neurons use ACh.
Sympathic post-ganglionic neurons use NE.

Generally the parasympathetic and sympathetic nervous systems work as antagonists.
For example: heart rate is increased by sympathetic stimulation and decreased by parasympathetic stimulation.
Integration of the nervous system
Neuronal communication can be excitatory or inhibitory, depending on the neurotransmitter released and the receptors present.
NE receptors called adrenergic receptors have been grouped in 4 categories, a₁, a₂, b₁ and b₂. Table 9.6 describes many effects.
Sympathic stimulation can increase heart rate (b₁ receptor) and relax skeletal muscle blood vessels (b₂ receptor) and constrict the urethral sphincter (a₁ receptor).

An action potential in one neuron does not necessarily result in an action potential in a post synaptic neuron.
The effect at the axon hillock is a summation of all local potential changes at the dendrites.

Summation can be temporal or spatial.
e.g. the closer an excitatory synapse is to the axon hillock the greater its effect on reaching threshold.
e.g. the more frequently neurotransmitter is released the greater effect on membrane potential.

Neuronal connections (hard wiring) determine sensitivity. One neuron can have 1000's of terminal boutons that all receive an AP.
One neuron can contact 1 or 1000s of other neurons.
One neuron could receive input from 1 or 1000s of other neurons.
Endocrine/nerve intergration
Norepinephrine (sympathetic NS) is very similar structurally to the hormone epinephrine released by the adrenal medulla. They can bind to the same receptors and induce the same effects.

Electrical Synapses
Electrical synapses are present between some neurons and between some neurons and glial cells. These cells are connected by gap junctions. Changes in ions in one cell are transmitted to the second cell through the gap junction. Electrical synapses allow rapid transmission of an AP from one to another. They have been identified in the retina and parts of the cerebral cortex.
The vast majority of synapses between neurons are chemical synapses.

Pharmacology Note
The common insecticide malathion is an acetylcholinesterase inhibitor. Poisoning results in, amongst other things, excess acetylcholine ACh in neuromuscular junctions and over stimulation of skeletal muscles.

Botox is a form of the the toxin from the bacterium Clostridium botulinum. Botulism is benerally caused by eating food contaminated with this bacterium. Botulinum toxin (a protein) blocks the release of acetylcholine ACh at neuromuscular junctions. Poisoning can result in death due to inactivity of respiratory muscles. Botox is used cosmetically to relax muscles in the face to reduce wrinkles!

Saxitoxin is produced by some marine Dinoflagellates that can bloom under certain conditions and result in "red tides". Saxitoxin can be absorbed by humans directly but more commonly poisoning occurs from eating shellfish that accumulate and concentrate the toxin. The toxin blocks voltage gated sodium channels in neurons causing systemic neorological effects. A similar neurotoxin is found in blowfish, a delicacy in Japan.

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This webpage was created by Peter King. Please contact the the author with comments at pking@fmarion.edu.
Last edited July 20, 2010.
http://people.fmarion.edu/pking/humanphys/nerves.html
copyright Peter King.