BIO 1121: Neuromuscular System & Neurons

• Neuromuscular system membrane potential will be covered
• BIO 1121: Anatomy & Physiology I

Structural Organization of Nervous System

• Central Nervous System (CNS) includes the brain & spinal cord
• Peripheral Nervous System (PNS) includes nerves & cranial nerves

General Function of Nervous System

• The nervous system collects information
• The nervous system processes & evaluates information
• The nervous system initiates response to information

Neuron Function

• Sensory neurons are afferent, they "Arrive"
• Motor neurons are efferent, they "Exit"

Characteristics of a Neuron

• Neurons have extreme longevity, up to 100 years
• Neurons are Amitotic, do not go through cell division
• Neurons have a high metabolic rate, requires oxygen and nutrients
• Neurons have irritability, able to respond to stimuli

Review of Nervous Tissue

• Consists of cells called neurons
• Neurons receive, process, and transmit nerve impulses
• Glial cells are supporting cells of the neuron
• Nervous tissue is vascularized

Components of Neuron

• Dendrites are short, numerous processes that receive incoming signals
• The Cell Body houses nucleus and organelles
• The Axon is a single long process that carries outgoing signals

Myelin Sheath

• Fatty insulation that surrounds some nerve fibers (axons)
• Electrically insulates axon
• Saltatory conduction is the "jumping" of action potential
• Schwann cells in PNS produce myelin
• Oligodendrocytes in CNS produce myelin
• Nodes of Ranvier are gaps in myelin sheath

Myelination by Schwann Cells

• Myelin is produced in the PNS by Schwann Cells
• A single axon at a time is myelinated

Myelination by Oligodendrocytes

• Myelin is produced in the CNS by Oligodendrocytes
• Multiple Axons are myelinated at a time

Unmyelinated Axons

• Have no myelin
• Conduct nerve impulses at slower speeds
• Connect neurons to the autonomic nervous system (ANS)
• ANS controls involuntary movement of smooth muscles

Multiple Sclerosis

• Autoimmune disorder with progressive demyelination of neurons in CNS
• Oligodendrocytes are attacked by immune cells
• Repeated inflammatory events cause scarring and permanent loss of function
• There is no cure, medicine is used to slow progression and occurrence of symptoms

Guillain-Barre Syndrome

• Rare autoimmune disease of the PNS
• Characterized by loss of myelin from peripheral nerves due to inflammation
• Muscle weakness begins in distal limbs and advances to proximal muscles
• Linked to campylobacter jejune infection and the flu
• Most function is recovered with little medical intervention

The Synapse

• The axon terminal will then synapse with another neuron or a muscle or gland cell
• The synapse contains a small space between nerve cells or another muscle, gland or organ

Neuromuscular Junction

• The specific space between a neuron and muscle cell

Neuron Classification

• Multipolar neurons: Many dendrites, one axon

• Multipolar neurons are the most common type of neuron

• Most interneurons are multipolar

• Bipolar Neurons: One dendrite, one axon

• Special sense neurons are Bipolar

• Unipolar Neurons: One single long axon (T formation)

• Most sensory neurons are unipolar

• Anaxonic Neurons: No axons, only dendrites

• Interneurons are anaxonic

Excitability

• The ability to change from relaxed to contracted based on electrical properties at their plasma membrane
• Skeletal, cardiac, & smooth muscle all exhibit excitability
• Skeletal muscle is voluntary
• Cardiac & Smooth muscle is involuntary
• Unconscious parts of nervous system can influence excitability, along with hormones
• Neurons have 2 jobs: Irritability & Conductivity
• Irritability will stimulate and cause an action potential
• Conductivity will conduct that action potential to another neuron or effector

Nerve Membranes

• Epineurium: covers entire nerve
• Perineurium: covers bundled axons called a fascicle
• Endoneurium: covers each individual axon

Motor Neuron & Motor Unit

• Neurons control skeletal muscle cells by transmitting signals from the brain or spinal cord.
• The axons of motor neurons divide and innervate skeletal muscles fibers; creating a motor unit
• Size of motor unit is inverse to degree of control
• Recruitment of motor units determines strength

Plasma Membrane of Neurons

• Neurons transmit electrical signals to perform bodily functions

• This includes various types of pumps and channels in the plasma membrane

• Pumps maintain specific concentration gradients by moving substances against the gradient

• Na+/K+ pumps account for 2/3 of a neuron's energy expenditure

• Ca2+ pumps

• Channels provide a passage for substances to move down its concentration gradient

• Leaky (passive) channels are always open

• Chemically gated channels are closed, require neurotransmitter

• Voltage-gated channels open in response to change in electrical charge across membrane

Cell Membranes (Review)

• Nerve cells contain a phospholipid bilayer
• Proteins determine what can move into and out of a cell
• Integral proteins are always open (leaky), typically K+
• Gated channels (voltage or ch regulated), typically Na+
• The nerve cell membrane can change polarity through movement of ions in order to send/receive a message

Neuron Channels

• Chemically Gated channels are located within cell body and dendrites
• Chemically Gated channels require neurotransmitter/chemical to activate
• Voltage Gated channels are located within axon hillock and axon
• Voltage Gated channels require specific voltage change to activate

Neurons at Rest (Polarized)

• Ion Concentration Gradient for K+, Na+, Cl-

• The cell has more K+ in cytosol compared to surrounding area

• The the cell has more Na+ & Cl- in interstitial fluid compared to surrounding area

• The cell uses the sodium-potassium pump (3 Na+ OUT, 2 K+ IN)

• There is a Ca2+ gradient at synaptic knob

• More Ca2+ is located in interstitial fluid compared to that in the cell.

• Gated Channels are closed

• There is an Electrical gradient difference across plasma membrane

• The Cytosol (inside cell) is negative

• The Interstitial fluid (outside cell) is positive

• Neurons at rest have a Resting Membrane Potential of negative 70 mV

Graded Potential

• Small, short-lived changes in RMP

• Established in dendrites & cell body by opening chemically gated channel

• Neurotransmitters released from pre-synaptic neurons cause graded potential

• The graded potential will Last as long as channels are open and until local ion current ceases

• The amount of change of graded potential depends change magnitude of stimulus

• Change depends upon type of channels open

• Graded potential Decays as it moves over distance

Graded Potential Direction of Change

• Na+ (cation) channels allow Na+ to enter the neuron: inside of neuron becomes more POSITIVE

• Ex. -70 mV to -50 mV = Depolarization

• K+ (anion) channels allow K+ to exit the neuron: inside of neuron becomes more NEGATIVE

• Ex. 30 mV to -60 mV = Hyperpolarization

Threshold

• Point where enough graded potentials cause neuron to conduct an action potential
• Requires a Depolarizing graded potential
• Threshold is approximately -55 mV
• Will cause Voltage-gated Na+ channels to OPEN

Excitatory Post-Synaptic Potential (EPSP)

• Depolarization
• Increases likelihood of an action potential (AP)
• i.e. "Excites" the next neuron

Inhibitory Post-Synaptic Potential (IPSP)

• Hyperpolarization
• Makes the postsynaptic membrane less likely to have an action potential (AP)
• i.e. "Inhibits" the next neuron

Summation

• Occurs when the changes in membrane potential from both EPSPs and IPSPs are added together
• Once added together, the graded potential must reach -55 mV to open the voltage-gated channels at the axon hillock
• Spatial Summation is when multiple presynaptic neurons release NT @ various locations onto dendrites and cell body
• Temporal Summation is when a single presynaptic neuron repeatedly releases NT at same location within a short period of time
• Both spatial and temporal summation occur at the same time
• The graded potential reaches the axon hillock depending if reach threshold or to inhibit threshold
• If threshold is reached, an action potential (AP) is initiated down the axon!

All-or-None Law

• If threshold is reached, an AP is initiated and propagated along the axon without decreasing in intensity
• If threshold if not reached, an AP is not initiated

Action Potential

• Occurs the total length of an axon
• Involves Depolarization & Repolarization

Depolarization

• Gain of positive charge within a neuron that changes membrane potential from negative to positive
• Opening of voltage-gated Na+ channels, causing an influx of sodium INTO the neuron

Repolarization

• Return of polarity from changing membrane potential from positive to negative
• Opening of voltage-gated K+ channels, causing an efflux of K+ OUT of neuron

Steps of Action Potential

• Some stimulus occurs and the resting membrane is at negative 70mV

• Chemically gated Na channels open on the dendrites and cell body

• Na+ enters the nerve cell

• The inside is now more positive, the threshold of negative 55 mV is reached

• Voltage gated Na+ channels at the axon hillock open up and voltage gated K+ channels start to open

• Na+ enters the axon, making the charge in there more positive at +30mV

• This is called the depolarization phase of the action potential

• Next, voltage gated K+ channels fully open at + 30 mV

• K+ leaves the axon, causing the voltage to go back down to negative 70mV

• This is called the repolarization phase of the action potential

• The voltage is good now, but the ions (Na+ and K+) are in the wrong places

• The Na+/K+ pumps will need to be used to fix the ion concentrations

• These pumps pump 3 Na+ back out of the axon and 2 K+ back in to the axon

• This whole thing (steps 4-9, the action potential) just happened on one small section of the axon

• once it happens, it will travel down the entire length of the axon, to the axon terminal

• It can travel by local conduction if the axon does NOT have myelin

• It can travel by saltatory conduction if the axon has myelin

• When the action potential gets to the axon terminal, it causes the release of a chemical called a neurotransmitter

• The neurotransmitter will then bind to a receptor on the next cell, the postsynaptic cell

• That will cause chemically gated channels to open on the postsynaptic dendrites or axon

• That then starts the whole process (back to step 1) on that next neuron

Refractory Period

• Brief period after an AP has been initiated during which an axon is either incapable of generating another action potential or a greater than normal amount of stimulus required to generate another AP
• The Absolute Refractory Period is when no amount of stimulus can initiate another AP
• The Relative Refractory Period is when another AP can be initiated, only if stimulus is greater than normally needed
• Occurs after absolute refractory period & during hyperpolarization phase

Propagation of Action Potential

• Myelin sheath along axon allows for saltatory conduction
• Action Potential “jumps” its signal along unmyelinated portions.

Synapse

• AP has traveled all the way down the axon!
• This is the portion of a neuron and its function is to release a neurotransmitter from synaptic vesicles
• Voltage-gated Ca2+ channels are located here
• More Ca2+ is located outside synapse than inside

Steps of Synapse

• Nerve signal reaches synaptic knob at end of axon
• Voltage-gates Ca2+ channels open and the Ca2+ moves into the synapse
• NT released due to binding of Ca2+ proteins on synaptic vesicles
• NT attaches to ligand (chemical) gated channels by diffusing across synaptic cleft to either another neuron or organ

Acetylcholine (ACh)

• Acetylcholine is the neurotransmitter of the neuromuscular junction which regulates voluntary movements
• Acetylcholine causes an EPSP

After Neurotransmitter Binds

• Neurotransmitter is quickly removed from the synaptic cleft by the following mechanisms:
  • Diffusion
  • Reuptake, ex. neurotransmitter serotonin is taken back to the presynaptic neuron by reuptake
  • Degradation by synaptic enzymes
  • ex. the neurotransmitter acetylcholine is broken down to acetate and choline by the enzyme acetylcholinesterase

Myasthenia Gravis

• Autoimmune disease, 1 in 10,000 people
• Primarily affects women 20-40 yrs of age
• Person's own antibodies attack the neuromuscular junctions
• Specifically, ACh nicotinic receptors are targeted
• Causes nerve signals to be interrupted and not trigger skeletal muscle contraction
• Symptom is typically skeletal muscle weakness
• Face & eye muscles are attacked first
• Most patients have normal life span, but respiratory muscle paralysis can be life threatening