Nerve, Muscle, and Synapse Physiology

Neuroscience

• The study of the nervous system.

• The human body contains roughly 100 million neurons.

• Consists of two main parts: The Central Nervous System (CNS) and Peripheral Nervous System (PNS).

• Research includes genes and other molecules that are the basis for the nervous system, individual neurons, and ensembles of neurons that make up systems and behaviour.

Central Nervous System (CNS)

• Comprised on the cerebral cortex, cerebellum, brainstem, and spinal cord.

Peripheral Nervous System (PNS)

• Peripheral nerves.

• For example, the axons of nerve cells which connect the spinal cord to the muscles are located here.

The Stretch Reflex - Mallet

• If going to the doctor for a physical examination, the doctor will hit the tendon with a mallet.

• The tendon is connected to the quadriceps muscle. Tapping the tendon causes the muscle to stretch.

  • ∴ Activation of nerve impulses in special receptors located in the quadriceps.

The Stretch Reflex - Impulses

• The activation of nerve impulses in special receptors located in the quadriceps, these special receptors are called stretch receptors.

• The nerve impulses are sent back to the spinal cord along the sensory neurons.

• They activate another nerve cell which feeds back out into the quadriceps.

• This activates another muscle causing contraction.

  • “A knee-jerk” reaction.

Natural Reflex - Biceps

• The example is holding a bag.

• The bicep muscle will be stretched based on the activation.

• If something is added to the bag, there is a slight shift downwards, causing the biceps to stretch.

• The degree of activation for the biceps feeds back onto the muscle and allows the arm to stay at 90°.

• This stretch reflex is used often and controls posture and muscle tone.

Withdrawal Reflex

• Touching a hot stove would activate this reflex.

• It is a standard reflex, slightly more complex than the stretch reflex as more cells are involved.

• The main process is the same. Your get activation of nerve fibers in the periphery with the withdrawal reflex.

• Sends a nerve impulse from the affected area to the spinal cord, where interactions with other neurons occur.

Neurons

• A type of cell that receives and sends messages from the body to the brain and back to the body.

• 10% of cells in the CNS, but they occupy 50% of the volume.

  • ∴ much bigger than glia.

• Three different types: afferent, efferent, and interneurons.

Afferent Neurons

• Carry information from periphery to the spinal cord via the dorsal roots.

• Make synaptic contact onto either efferent neurons directly, or the make excitatory contact onto interneurons.

• Afferent neurons always use the excitatory neurotransmitter glutamate.

Efferent Neurons

• Carry information from the spinal cord to the periphery via the ventral roots.

• They receive input from either afferent neurons directly or from interneurons to make contact onto muscle.

• Uses a excitatory neurotransmitter called acetylcholine.

Interneurons

• Carry information between neurons.

• Can excite or inhibit neurons.

• Located only in the CNS, either the spinal cord or the brain.

• Can receive input from afferent neurons, efferent neurons, or other interneurons.

• They output information onto other interneurons or onto efferent neurons.

Glia

• Acts as the glue, very numerous and tiny.

• Another type of neuron. 90% of the cells in the NS and ½ the volume in the NS.

• Three different types:

  • Oligodendrocytes, astrocytes, and microglia.

Oligodendrocytes

• Makes myelin which is important in action potential conduction in the CNS. Schwann Cells do this in the PNS.

• Crucial for myelin production.

Astrocytes

• Physically and metabolically support neurons by buffering extracellular K⁺, removing neurotransmitter, helping maintain the blood brain barrier, and plays a role in signalling and information processing.

Microglia

• Serve immune functions in CNS.

Intertwining Afferent and Efferent Neurons

• When afferent and efferent neurons innervate a muscle, they are separated around the muscle.

• As they travel toward the CNS, they intertwine (bundle) and travel within a mixed peripheral or spinal nerve.

• Before entering the spinal cord, they split: afferent fibers enter dorsally, while efferent fibers exit ventrally.

• Information goes in via afferent fibers to the CNS and leaves the CNS via efferent fibers.

Reflex Loop

• The activation of a receptor activates a afferent fiber. The information comes through the dorsal horn.

• The efferent neurons, located in the ventral spinal cord, leaves the ventral area.

  • Afferent comes through dorsal part of the cord.

  • Efferent comes through the ventral part of the cord.

• The efferent fiber then activates a muscle.

White Matter

• Within the white matter of the spinal cord, myelinated axons of neurons which are travelling up or down the spinal cord.

• This is why white matter appears white.

  • It contains myelinated axons, giving a white appearance.

Grey Matter

• Contains cell bodies of interneurons and unmyelinated processes.

• The lack of myelin makes it look grey.

The Stretch Reflex - Afferent Neurons

• Tendon tap of the patellar tendon results in stretching of the quadriceps muscle.

• Stretching of the muscle activates stretch receptors attached to afferent neurons.

• The afferent neurons will travel together with the efferent neurons in the mixed peripheral nerve until it is outside the spinal cord.

• Step 1.

The Stretch Reflex - Interneurons

• Branches of the green, afferent nerve fiber also end on the red inhibitory interneurons (in this specific reflex, the interneurons are inhibitory).

• When activated, the interneurons inhibit efferent neurons which innervate the hamstrings.

• This inhibits contraction of the hamstrings muscle which would otherwise interfere in reflex response.

• Step 2.

The Stretch Reflex - Efferent Neurons

• The afferent neuron takes a separate pathway from the efferent neuron and enters through the dorsal root of the spinal cord.

• Connects with a efferent neuron in the ventral part of the spinal cord and sends a synapse.

• Efferent neurons coils through the ventral root of the spinal cord, travels the mixed peripheral nerve to the quadriceps, resulting in contraction.

• Step 3.

Agonistic and Antagonistic Pair

• All muscles have a opposing-function pair.

  • i.e. biceps (agonistic) → lifts forearm, triceps (antagonistic) → extends forearm.

• Coordinated movement is controlled by innervation and activation of agonist/antagonist muscles.

Dendrites

• Receive information either from the periphery or from other cells.

• Receive stimuli through activation of chemically or mechanically gated ion channels; in sensory neurons, produce generator or receptor potentials; in motor neurons and association neurons, produce excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs).

Nucleus

• Genetic material factory.

Axon

• Propagates (conducts) nerve impulses from initial segment (or from dendrites of sensory neurons) to axon terminals in a self-reinforcing manner

• Impulse amplitude does not change as it propagates along the axon.

Axon Hillock

• Input coming into the dendrites is integrated in the axon.

• An impulse is initiated here if there is enough input for a nerve impulse.

• Trigger zone; integrates EPSPs and IPSPs and, if sum is a depolarization that reaches threshold, initiates action potentials (nerve impulse).

Synaptic/Axon Terminals

• Contains neurotransmitters.

• The neurotransmitter will be released and cause other cells/muscle to be activated or inhibited.

• Inflow of Ca²⁺ caused by depolarizing phase of nerve impulse triggers neurotransmitter release by exocytosis of synaptic vesicles.

Cell Body (soma)

• Contains ribosomes.

• Has all the information and machinery to manufacture proteins.

• Receives stimuli and produces EPSPs and IPSPs through activation of chemically or mechanically gated ion channels

Direction of Flow

• Information in the nervous system flows in one direction.

• It goes from the dendrites to the axon, ending at the synaptic terminal.

• It will never flow in the opposite direction.

Presynaptic & Postsynaptic Neuron

• The presynaptic neuron sends the signal.

• The postsynaptic neuron receives the signal.

• A neuron can be postsynaptic to one cell and presynaptic to another cell.

Bipolar Cell

• A specialized type of nerve cell characterized by having one dendrite and one axon extending from the cell body.

• It has two distinct processes, emerging from the cell body.

  • These extensions are one axon and one dendrite.

Pseudo-Unipolar Cell

• Has one axon that splits into two branches.

• These branches act as both dendrites and axons, with one branch carrying signals to the periphery and the other to the CNS.

• Afferent neurons of the stretch reflex fall into this category. 

Multipolar Cells

• Characterized by a single axon and multiple dendrites extending from their cell body.

• This structure allows them to receive and integrate a large amount of information from other neurons.

• All of them have a axon terminal that terminate in the muscle, affecting activity in the muscle.

• Both interneurons and efferent neurons are this type.

Pseudo-Unipolar Function

• Peripheral Axon

  • The peripheral axon extends from the cell body to the muscle. Acts like the dendrites.

• Central Axon

  • Extends from the cell body to the CNS.

  • Acts like a normal axon and makes contact with other axons on interneurons.

• Dorsal Root Ganglion

  • The cell body of the neuron is located here.

Myelin

• A fatty, insulating sheath that surrounds the axons of neurons.

  • A lipid-protein mix; 80% lipid and 20% protein.

• The white fatty myelin is made of either oligodendrocytes or Schwann cells.

• Ingredients: myelin basic protein, proteolipid protein, and glycolipids.

• Increases the speed of electrotonic conduction.

The Stretch Reflex - Pseudo-Unipolar (Afferent)

• The afferent neuron is a pseudo-unipolar cell, receiving input via the peripheral axon and providing output to the CNS via the central axon.

• There are two synapses that the pseudo-unipolar neuron makes.

The Stretch Reflex - Multipolar Neuron (Efferent)

• During the stretch reflex, the afferent neuron makes direct monosynaptic contact onto a efferent neuron (red)

• The efferent neuron innervates the quadriceps.

• The activation of this excitatory efferent neuron results in the quadriceps contracting.

The Stretch Reflex - Multipolar Neuron (Inter.)

• The afferent neuron is excitatory and activates this inhibitory interneuron (green).

• Makes contact onto a efferent neuron (black).

• The efferent neuron innervates the antagonistic muscle, for quadriceps its the hamstring.

• The inhibitory interneuron inhibits the efferent neuron to the hamstring, preventing the hamstrings from contracting.

Neuronal Membrane

• A phospholipid bilayer, impermeable on it own, but has protein pumps and channels embedded in it.

• The most important protein pumps/channels for setting resting membrane potential are the Na⁺/K⁺ pump and the Na⁺ and K⁺ leak channels.

Neuronal Pumps and Channels

• Controls movement of ions through membrane.

  • Pumps: active transport.

  • Ion channels.

• Passive channels (leak channels).

• Gated channels: ligand-gated and voltage-gated.

Active Transport

• Use an energy source (ATP) and is not driven by a concentration gradient.

• Neurons specifically.

Ion Channels

• Does not use a energy source (ATP).

• Acts as a door which is either open or closed.

• Allows the flow of ions down its concentration gradient.

Pumps and Channels Characteristics

• There is many different types of protein pumps and channels, all with different characteristics.

• Due to the presence of pumps & channels, there is a uneven distribution of different ions inside and outside the cell.

  • Gives the cell a resting membrane potential (RMP).

  • Charge separation b/w the ECF and ICF.

Leak Channels (Passive Channels)

• A channel that is always open. Allows the the passive flow of ions into/out of the neuron.

• Allow diffusion of ions down their electrical and chemical concentration gradients in an attempt to reach equilibrium.

• Selective: each ion has its own channels which they can pass.

• Two forces acting on each ion: chemical and electrical gradient.

Ligand-Gated Channel

• A neurotransmitter binds to its receptors, leading to conformation change (close → open), allowing the flow of ions through them.

• The ligand is the neurotransmitter.

  • Into/out of the cell.

Voltage-Gated Channels

• Open and close in response to changes in the electrical potential across the cell membrane.

• These channels are crucial for generating and propagating action potentials.

Resting Membrane Potential (E_m or RMP)

• Steady-state condition determined by relative permeability of membrane to K⁺ and Na⁺.

• Measure of electrical potential different between ICF and ECF.

• Due to the activity of the Na⁺/K⁺ pump, there is an uneven distribution of Na⁺ and K⁺ across the membrane.

  • ∴ Charge separation, approx. -70mV.

• Ions involved in setting RMP:

  • K⁺, Na⁺, [Cl⁻, organic anions (-)].

• Pumps/channels involved in setting RMP:

  • Na⁺/K⁺ pump, Na⁺ leak channels, K⁺ leak channels, [Cl⁻ pump].

Net Negative Charge

• Na⁺/K⁺ pump is electrogenic, moving charge across the membrane.

• Requires energy obtained from the hydrolysis of ATP (an energy carrying molecule) to ADP + P_i.

• 3 Na⁺ molecules move out of the cell, 2 K⁺ molecules move into the cell.

  • Results in a net negative charge inside the cell.

• Moving a net +1 ion charge out of the cell for every cycle in the Na⁺/K⁺ pump, resulting in a net negative charge.

Na⁺/K⁺ ATPase

• 3 Na⁺ bind to the Na⁺/K⁺ pump.

• ATP binds to the pump causing conformation change in the protein, leaving a phosphate group attached to the protein and ADP.

• The energy that comes from hydrolysis results in a change of conformation of the change Na⁺/K⁺ pump.

• The phosphate group leaves, resulting in conformation change, taking in 2 K⁺.

Na⁺/K⁺ Pump Creates Gradients

• Both chemical and electrical gradients are present.

  • For the electrical gradient, the intracellular environment wants to become more positive.

• The Na⁺/K⁺ pump pumps K⁺ into the cell, and the K⁺ then wants to move back out of the cell.

• The Na⁺/K⁺ pump pumps Na⁺ out of the cell, which then wants to move back into the cell.

Equilibrium

• At any time you have a gradient for a ion across a membrane, you will have more ions on side of the permeable/semi-permeable membrane.

• The cell will try to reach a state of equilibrium; equal distribution.

Potassium Leak Channel

• There is more K⁺ in the cell than outside the cell.

• The chemical force pushes K⁺ outside the cell through the leak channel.

• The electrical force pushes the K⁺ into the cell (as a positively charged ion).

  • Both of these forces act on K⁺ at the same time.

• Net charge in the ICF is negative, ECF is positive.

Equilibrium Potential

• The membrane potential at which the chemical concentration gradient is balanced.

• No net movement of any ions into or out of the cell because the chemical and electrical force are equal and acting in opposite directions.

  • Cancels out.

• Na⁺ and K⁺ attempt to reach an ideal potential, +55mV and -90mV respectively.

  • Can be calculated using Nernst equation.

Equilibrium Potential for Potassium

• No net movement of K⁺ into or out of the cell.

• The chemical force and the electrical force are equal and acting in opposite directions.

• With the Nernst equation, you can calculate the equilibrium potential of an ion, based on the amount present, temperature, etc.

Potassium at Resting Potential

• K⁺ will be moving out of the cell.

• K⁺ is a positively charged ion and the E_m is -70mV, K⁺ will move to try to bring the E_m of the cell to -90mV.

  • -90mV is equilibrium potential that K⁺ wants to maintain.

• ∴ Net movement is out of the cell, taking with it the positive charge.

Sodium Leak Channel

• There is more Na⁺ outside the cell than the inside.

• The chemical force acts to push Na⁺ into the cell, to achieve a state of equilibrium.

• The electrical force acts to push Na⁺ into the cell.

• Net charge inside the cell is negative, and the net charge outside the cell is positive.

Sodium at Resting Potential

• Na⁺ will be moving into the cell.

• At a RMP of -70mV, Na⁺ will move to make it equal to its equilibrium potential of +55mV.

• Neither K⁺ or Na⁺ are successful in shifting the membrane potential to its equilibrium membrane potential.

Equilibrium Channel for Sodium

• If the inside of the cell was +55mV, the electrical force would push positively charged Na⁺ out of the cell while the chemical force would push Na⁺ into the cell.

• The forces acting on Na⁺ would be equal and opposite, resulting in no movement of Na⁺ into or out of the cell.

  • Na⁺ would be at equilibrium.

Leak Channels and E_m Rule

• Na⁺ alone would force RMP to +55mV.

• K⁺ alone would force RMP to -90mV.

• The more permeant the ion, the greater its ability to force E_m towards its own equilibrium potential.

• The more permeable a membrane is to a specific ion, the closer the cell’s RMP will be to that ion’s equilibrium potential.

Leak Channels and E_m Ions

• There is more K⁺ leak channels in the membrane, so the RMP is closer to the equilibrium potential for K⁺.

• Permeability is 50-100x times greater to K⁺ than Na⁺.

• E_m is therefore closer to E_K⁺ → more leak channels for K⁺.

E_m Variability

• The variable values for RMP is because there are different amounts of leak channels in different cells.

• The specific ratio of Na⁺ and K⁺ determines the RMP of a given cell.

  • ∴ Subject to variability.

RMP Summary

• Activity of Na⁺/K⁺ ATPase causes intracellular environment to be negatively charged with respect to extracellular environment (3 Na⁺ out/ 2 K⁺ in).

• At RMP passive ionic fluxes are balanced so that there is charge separation and E_m remains constant.

• Value of RMP (-70mV) is closest to equilibrium potential of the ion with greatest membrane permeability (K⁺).

RMP Ion Movement

• At RMP, there is movement of ions (K⁺ and Na⁺) across the PM.

• K⁺ is pumped into the cell by the Na⁺/K⁺ pump and is leaving through K⁺ leak channels.

• Na⁺ is pumped out of the cell via the Na⁺/K⁺ pump and coming back into the cell via Na⁺ leak channels.

  • Less Na⁺ is coming out of the leak channels.

• End result of ion movement = -70mV.

Action Potential

• A large change in membrane potential from -70mV to +30mV and back to resting over a period of a few milliseconds.

• An electrical signal is generated due to activity of voltage-gated Na⁺ and voltage-gated K⁺ channels.

• Opening of these channels results in a ion flow and membrane potential changes.

• Occurs when specific stimuli (physical or chemical) disrupt RMP, causing ion-selective channels to open.

Afferent Activation

• Muscle stretch (stretch reflex) or other sensory stimuli increase opening of specialized Na⁺ receptors.

  • Allows Na⁺ entry into the afferent fiber and depolarizes the neuron.

• If depolarization reaches threshold (~ -50 mV), voltage-gated Na⁺ channels open and an action potential is generated.

Stretch Receptor

• Embedded in the muscle. There is a receptor at the tip of the afferent neuron.

• It senses muscle stretch (i.e. stretch in the quadriceps muscle).

Stretched/Unstretched Sensory Receptor

• When the muscle is not stretched, the Na⁺ cannot casually flow inside as it is too large.

• When the muscle is stretched, the sensory receptor enlarges.

• When this occurs, the Na⁺ can go through the pores of the receptor.

  • Increased Na⁺ permeability.

• Goes from the ECF to the ICF.

Threshold Potential

• A value of membrane potential that must be reached for a action potential.

• This value is needed for the opening of voltage-gated Na⁺ channels and firing a action potential.

• Threshold varies slightly between cells but is typically 10–15 mV more depolarized than the RMP.

Slight Depolarization

• Following tendon tap, the quadricep muscle stretches, allowing the sensory receptors to stretch and allow Na⁺ entry into the cell.

• Cell depolarizes slightly.

• If the threshold number is reached (~-50mV), the voltage-gated Na⁺ channels will open completely.

Ion Channels at RMP

• The voltage-gated Na⁺ channel and the voltage-gated K⁺ channel are closed at rest.

• The Na⁺/K⁺ ATPase is still functioning, keeping K⁺ inside the cell and Na⁺ outside the cell.

• Leaky channels are still open.

Depolarization

• When the threshold potential is reached, the voltage-gated Na⁺ channels open, removing the activation gate.

• When Na⁺ moves into the cell. The internal compartment of the cell changes from being negatively charged to positively charged.

  • +30mV.

• Brings the membrane potential closer to Na⁺ equilibrium potential (+55mV).

Peak

• After reaching +30mV, the Na⁺ channel closes; the inactivation gate slides across the pore and blocks more Na⁺ from entering the cell.

  • 1-1.5 ms.

• Open conformation of the voltage-gated Na⁺ channels is only maintained for a few milliseconds.

Repolarization

• After the inactivation gate blocks off the Na⁺ channel, the activation gate of the K⁺ channel unblocks the channel.

• K⁺ rushes outside the cell to make the inside of the cell equal to its equilibrium potential (-90mV).

  • K⁺ has a positive charge, so it would leave the cell to make the ICF negative.

• However, overshoots it a bit.

Hyperpolarization

• Membrane potential decreases, the value going closer to the RMP value as K⁺ is leaving the cell.

• The permeability of the membrane to K⁺ is greater during hyperpolarization than it is at RMP.

  • The membrane is more permeable to K⁺.

• This is b/c the leak channels are open (where K⁺ can flow) and there are voltage-gated K⁺ that are open.

Absolute Refractory Period (3, 4)

• Cannot fire an action potential in response to any stimulus.

• Voltage-gated Na⁺ channels are either open or inactivated.

• The inactivation gate blocks the voltage-gated Na⁺, closing off the pore.

• The channel cannot reopen until the gate leaves the pore and the membrane repolarizes to close it.

• After the channels have recovered, another AP can occur.

Relative Refractory Period (5)

• Possible to generate a AP, but extremely difficult.

• This is because voltage-gated K⁺ channels are still open.

• For the cell to reach the threshold (-50 mV) where voltage-gated Na⁺ channels open, Na⁺ permeability must exceed K⁺ permeability, which is already elevated due to open voltage-gated K⁺ channels.

Action Potential Table

Condition	Reason for Change in Potential	Relative Permeability
1. Rest		K⁺ » Na⁺
2. Depolarizing Input	Sensory of synaptic stimulation	Slight ↑ to Na⁺
3. Start of AP (depol)	V-gated Na⁺ channels open	Na⁺ »» K⁺
4. Repolarizing Phase	V-gated K⁺ channels open & Na⁺ channels inactivate	K⁺ »» Na⁺
5. End of AP	V-gated Na⁺ channels at rest & V-gated K⁺ channels still open	K⁺ »»»» Na⁺
6. Rest	V-gated K⁺ channels at rest	K⁺ » Na⁺

Membrane Conductance

• A measure of how easily ions can flow across the membrane, represented by ‘g’.

• At the beginning of a AP, there is a increase in Na⁺ conductance.

  • This tapers off quickly.

• At the beginning of a AP for K⁺, there is a slight delay before there is a K⁺ conductance increase (opening of K⁺ voltage channels).

  • Tapers off.

Action Potential: Transmission

1. Axon at resting membrane potential.

2. Activation results in opening of voltage-gated Na⁺ channels, local depolarization of membrane.

3. Local depolarization of membrane causes adjacent voltage-gated Na⁺ channels to activate.

4. New action potential is generated in adjacent membrane.

5. Action potential only travels in one direction due to refractory period.

Adjacent Segments

• AP begins with Na⁺ flowing into the cell as a response from a stretched sensory receptor.

• Once the threshold is reached, the Na⁺ voltage-gated channels open, causing local depolarization in a segment of the axon.

• Depolarizes the neighbouring membrane to threshold, activating a AP.

• The AP is transmitted from segment to segment in a adjacent, one direction manner.

Electrotonic Conduction

• Spread of current inside axon.

• AP initiated at one point in membrane. The current spreads electronically to adjacent membrane.

• The adjacent membrane depolarizes to threshold and a new AP generated in adjacent membrane.

• Proceeds in one direction only.

Time Needed for Electrotonic Conduction

• Flow is fast but the AP must be regenerated at every point on the membrane. This requires opening and closing of channels, which takes time!

• Moreso if the axon is long, which will take more time for the signal to travel.

• The removal of our foot from a nail (as an example) has to be fast. In reality, the removal of our foot is ½ seconds.

  • Due to myelination.

Myelination

• Speeds up AP propagation along the membrane of a neuron.

• Virtually all efferent neurons are myelinated.

• The production of myelin stem from the glia.

• It is wrapped around the neuronal axon.

Oligodendrocytes - Myelin

• Makes myelin in the Central Nervous System (CNS) only.

  • i.e. interneuron.

• A single oligodendrocyte is able to myelinate several axons and able to myelinate several regions within a given axon.

• In the figure, its responsible for myelinating two different neurons.

• Potentially able to lay down 7 different myelinated regions in total.

Schwann Cells - Myelin

• Makes myelin in the Peripheral Nervous System (PNS) only.

  • i.e. efferent neuron.

• Produced in the nucleus.

• Each myelinated segment is generated by a different Schwann cell.

Unsheathing the Axon

• Over time, the myelin produced by Schwann cells/oligodendrocytes wraps itself around the axon.

• This protein-lipid mix wraps around the axon of a neuron and acts as a insulator.

Myelin Location

• Is only found wrapped around the axon.

• There is no myelin around the cell body or the dendrites of a neuron.

• Myelin stops right before the synaptic terminals.

• Begins right after the initial segment of the axon until the axon branches off at the synaptic terminals.

Nodes of Ranvier

• Unmyelinated regions of a myelinated axon.

• The voltage-gated Na⁺ channels are clustered here.

• There are very few voltage-gated Na⁺ channels along the axon in the myelinated region.

• The other area where voltage-gated Na⁺ channels are clustered is the axon hillock, which is also unmyelinated.

Myelin - AP Propagation

• Myelin speeds up AP propagation by acting as an insulator.

• It increases conduction speed by improving electrostatic efficiency, so the AP doesn’t need to be regenerated at every point along the membrane.

• Regeneration is required only at the nodes of Ranvier.

• The AP travels from node to node without diminishing in amplitude.

Myelin - Charged Environment

• The protein-lipid substance of the myelin surround and insulates the axon, preventing positively charged ions from entering from either outside of inside the membrane (in the myelinated region).

Myelin - AP Amplification

• If an AP is generated at the first node, it travels to the second node without decreasing in size, allowing the neighbouring tissue to depolarize without active depolarization along the entire axon.

• Neighbouring tissue doesn’t need to be depolarized at every point along the myelinated region because of myelin.

• Depolarization and the opening of voltage-gated Na⁺ channels occur only at the nodes of Ranvier.

• This reduces the need for AP regeneration.

Axon Propagation Speed

• There are two factors where determine the speed of an axon propagating a action potential.

  1. Size of an axon.

  2. Whether the axon is myelinated or not.

• The thicker an axon is, the faster a AP can propagate.

• Myelinated axons propagate AP faster than unmyelinated axons.

Multiple Scelerosis

• It is thought that the immune system attacks the myelin.

• This leads to the speed of saltatory conduction to decrease, as the myelin is not there to increase the speed of transmission.

  • Loss of myelin = decreased transmission speed.

Classification of Fiber Type

Fiber Type	Group 1	Group 2	Group 3	Group 4
Diameter	12 - 20µm	6 - 12µm	1 - 5µm	0.2 - 1.5µm
Speed	80 - 120m/s	35 - 75m/s	5 - 30m/s	0.5 - 2m/s
Sensory Receptors	Skeletal muscle Proprioceptor	Skin Mechanoreceptor	Pain/temperature	Pain/itch/temperature

• Action potential frequency: Fast →→→ Slow.

Proprioceptor

• Sensory receptors which sense the position of our limbs.

• Proprioceptors and efferent neurons are included among the thickest diameter neurons that are myelinated.

  • Conducts AP from 80 - 120m/s.

Mechanoreceptor

• Smaller than the larger fibers in the group (group 2).

• A type of afferent neuron.

  • i.e. how you know you’re touching your desk.

One Directional Propagation

• AP arrives at axon going from left to right; AP will always travel down the axon to the synaptic terminal.

• Absolute refractory period (ARP) lasts 2 milliseconds.

• By the time the ARP is over, action potential is between 2 - 20cm down the axon.

  • Far away enough that depolarization will not occur in neighbouring tissues.

Synaptic Transmission

• A physical stimulus causes a sensory neuron to fire an AP.

• This generates a receptor potential; the nerve ending depolarizes to threshold, and an AP is produced in the sensory neuron.

• The AP travels via electrotonic or saltatory conduction in the CNS.

• There's no direct connection between sensory neurons to muscles.

• Instead, the presynaptic neuron releases neurotransmitters from vesicles into the synaptic cleft.

• These neurotransmitters bind to the postsynaptic neuron, causing an excitatory or inhibitory response that ultimately leads to a physiological effect.

Gap Junction

• Allows ions and molecules to pass directly from cell to cell through an actual channel between cells.

• Allows for electrical synaptic transmission to occur.

• Typically connected at the dendrites.

  • Dendrite to dendrite, dendrite to cell body, or cell body to cell body.

• Found in dendrite/cell body area, where electrical transmission occurs.