NEUROCOMMUNICATION
CHAPTER 4
• The Parts
• Membrane
• Semipermeable
• Bilayer of lipids
• Channels; e.g., ionotropic
• Signals; e.g., metabotropic
• Pumps; e.g., Na-K
• Ions
• Cations & Anions
• Different forces on membrane
• Electrostatic pressure
• Concentration gradient
• Resting membrane
• Active membrane
• Membrane
• 2 forces cause Na+
pressure to enter
inside
• Electrostatic pressure
• Negative charge
inside membrane
(Anions) pulls on Na+
on the outside to
come inside
membrane
• Most Na+ can’t come
in because Na+
channel is closed
when membrane is at
rest
• Membrane
• 2 forces cause Na+ pressure to
enter inside
• Concentration Gradient
• Concentration of ions
will randomly diffuse
across the membrane
through respective ion
channels
• Ions will move from a
HIGH concentration to
a LOW concentration
• Brings balance of Na+
& K+ ions across the
membrane
RESTING
MEMBRANE:
HOMEOSTASIS
• Neuron at resting state
• Ions
• Na outside
• K inside
• Cl inside
• Membrane
• Electrical charge = -70 mV
• Sodium-potassium
transporter (pump)
• A protein in the
membrane
• Extrudes Na &
ingests K ions
• Helps to restore
homeostasis
POST SYNAPTIC (PSP)
MEMBRANE
• Potential changes in the electrical
charge inside the post synaptic
membrane (-72mv to -67mv)
• Increases/decreases probability of
AP
• Neurotransmitter binds with
post-synaptic receptors &
starts either:
• Mild depolarize (EPSP)
• Mild hyperpolarize (IPSP)
• Along the membrane
• Excitatory postsynaptic
potential (EPSP)
• Depolarization of
the postsynaptic
membrane
• Increase likelihood
of AP
• Range: -70mV to -
67mV
• Along the membrane
• Inhibitory postsynaptic
potential (IPSP)
• Hyperpolarization of
the postsynaptic
membrane
• Decreases
likelihood of AP
• Range: -70mV
to -72mV
PSP INTEGRATION
OF SIGNALS
• PSP (EPSP or IPSP) signals are
integrated (summed) at AIS over
space or time:
• Temporal summation
• PSP signals produced in
rapid succession at same
synapse sum up to a
stronger collective PSP
signal
PSP INTEGRATION
OF SIGNALS
• PSP (EPSP or IPSP) signals are
integrated (summed) at AIS
over space or time:
• Spatial summation
• Similar PSPs across
membrane sites sum
together to produce a
stronger collective PSP
signal
ACTION POTENTIAL?
• Graded summation of all
PSP signals occurs as
they approach the axon
initiating segment (AIS)
• Summation occurs at AIS
near axon hillock
• Possible summation
outcomes:
• EPSPs < IPSPs = No AP
• EPSPs > IPSPs = AP
ACTION POTENTIAL
• Initiating the AP
• Repolarization stage (~2ms)
• Na+ voltage-gate channel closed
• Na-K pump removes Na+
• K+ efflux continues
• K+ voltage-gate begin gradually closing
• This triggers hyperpolarization stage
• Hyperpolarization stage
• Efflux of K+ is pumped back inside by Na-K pump until resting
potential is once again achieved
• Ahh….at last!
• AP Refractory periods
• Absolute refractory (AR)
• Starts with initiation of AP
• AR ends ~ 1 ms after AP starts
• Impossible to start another AP
• Relative refractory (RR)
• Follows AR (~2 ms after AP
starts)
• Direction of neural firing cannot
be reversed
• Can fire again after AR is done,
BUT PSPs must be larger than
normal (resting membrane
potential)
• RR ends when homeostasis
returns
• ~3-4ms after initial AP
• Communication Between Neurons
• Structure of synapses
• Presynaptic membrane
• The membrane of a
terminal button that lies
adjacent to the
postsynaptic membrane
and through which the
neurotransmitter is
released
• Postsynaptic membrane
• The membrane located on
the dendrite of the neuron
that receives the
information
• At the terminal button
• Golgi complexes package
Neurotransmitter in vesicles
•
• Vesicles bind with membrane
wall
• Arrival of AP triggers influx of
Calcium ions
• The influx of calcium ions
releases (exocytosis)
neurotransmitter held in vesicles
into cleft
• FYI: Neurons often hold and
release a couple (2) coexisting
neurotransmitters
RECEPTORS
• Protein that contains binding
sites for neurotransmitters
• Many are on postsynaptic
membrane (except for
autoreceptors)
• 1 type of neurotransmitter
binds with many receptor
types
• Different receptor
subtypes in brain may
respond to same
neurotransmitter in
different ways
RECEPTOR
SUBTYPES
• Neurotransmitter will
activate either ionotropic
or metabotropic ligand
receptors that influence
postsynaptic neuron
response
• Ligand-activated
receptors
• Ligand = any
molecule (e.g.,
neurotransmitter)
that binds with
another molecule
RECEPTOR
SUBTYPES
• Ionotropic receptors
▪ → = attached to
▪ Neurotranmitter (1st
messenger) → IR
▪ Direct gating: effect of
ligand binding is FAST to
open or close the channel
and lasts for only a few
milliseconds
▪ Receptor function:
modulates neural
circuitry that produces
behaviour (e.g., fight or
flight)
RECEPTOR
SUBTYPES
• Metabotropic receptors
• Indirect gating: effect
of ligand binding is
SLOW to open channel
and lasts for seconds
or even minutes
• Receptor function:
• modulates behaviour
by altering the
excitability of
neurons (EPSP) and
the strength of
synaptic connections
• Think: LTP
(learn/memory)
RECEPTOR SUBTYPES
• Metabotropic receptors
• Signal Protein = serpentine
protein that winds across
membrane 7x
• G Protein = guanosine-
triphosphate-sensitive-protein
• It will either:
• 1. Move through
cytoplasm to bind with
nearby ion channel and
modulate ion activity and
induce EPSP or IPSP (see
A)
• OR….
RECEPTOR
SUBTYPES
• Metabotropic receptors
• 2. Trigger the synthesis of a
second messenger
• Diffusion of second
messenger influences
neuron function
• Example: Second
messenger enters the
nucleus to bind with
DNA that influences
genetic expression
• Communication Between Neurons
• Autoreceptor
• A receptor located on the same
neuron that responds to the
neurotransmitter that was just
released by that neuron.
Function:
• Regulate internal processes of
the cell
• Reuptake
• The re-entry of a neurotransmitter by a
terminal button brought back through its
membrane
• This terminates the postsynaptic
potential.
• Termination can also occur through
enzymatic degradation
GAP
JUNCTIONS
• Electrical Synapses
• Narrow spaces between
similar adjacent cells
• Cells linked by tubular
protein channels filled with
cytoplasm called connexon
• Allows small molecules and
electrical signals to pass
from cell-to-cell
• Transmit signals much faster
than chemical synapses
• Synchronize the activity of
similar cells in a particular
area
• Identifying Neurotransmitters
• 4 Criteria
• 1) Chemical must by synthesized or
present in neuron
• 2) In the active neuron the chemical must
be released and able to produce a
response in target cell
• 3) Same response must be obtained when
chemical is experimentally placed on
target cell
• 4) A mechanism must exist to remove
chemical from the site of activation after
activity is done
• Neurotransmitters
• Over 100 transmitters have been
classified
• Small Molecule Neurotransmitters
• Amino Acids
• Glutamate, Aspartate, Glycine, & GABA
• Monoamines
• Dopamine, Epinephrine, Norepinephrine, &
Serotonin
• Acetylcholine
• Unconventional
• Soluble-gases: e.g., Nitric oxide
• Endocannabinoids
• Large Molecule Neurotransmitters
• Neuropeptides
• Neurotransmitters
• Small Molecule Transmitters (SMT)
• Synthesized from diet
• SMT released from terminal
button can be replaced very
quickly at presynaptic
membrane
• Nutrients from diet converted
into SMT move through blood
stream into the neuron
• Neurotransmitters
• Small Molecule Transmitters (SMT)
• Common SMT
• Acetylcholine (ACh)
• Most common in nervous system.
• At junction of efferent motor
neurons.
• Activates skeletal muscles
• Inhibits heartbeat
• Choline will break down fats in
food – egg yolk, avocado, olive
oil….
• ACh releases into synapse
• then ACh-esterase is released to
detach Acetate from Choline for
re-uptake
• Neurotransmitters
• Common SMT (Monoamines –
catecholamines)
• Norepinephrine (NE, or noradrenaline)
• Excitatory transmitter for mammalian
heart
• Epinephrine (EP, or adrenaline)
• Excitatory transmitter for amphibian
heart
• Produced in the adrenal glands (above
kidneys)
• Dopamine (DA)
• Helps coordinating motor movement
• Loss related to Parkinson's disease
• Involved with addictions
• Neurotransmitters
• Common SMT (Monoamines - Indolamines)
• Serotonin (5-HT)
• Regulates
• mood and aggression
• appetite and arousal
• perception of pain, respiration, & sleep
• Derived from Tryptophan
• Tryptophan found in turkey, milk, bananas….
• Neurotransmitters
• Common SMT (Amino Acids)
• Glutamate (GLU) & Aspartate (Asp)
• Main excitatory neural transmitter
• Found throughout CNS
• Synthesized from glucose
• Non-essential AA
• Does not cross Blood-Brain Barrier
• Too much can damage neurons
• Glycine (GLY)
• Inhibits brain stem and spinal cord activity
• Neurotransmitters
• Common SMT (Amino
Acids)
• Gamma-aminobutric acid (GABA)
• Main inhibitory neural
transmitter
• Histamine (H)
• Arousal/waking, constrict
muscle, constrict
airways…..
• Neurotransmitters
• Transmitter gases (Small Molecule Transmitters)
• Nitric oxide (NO) and Carbon monoxide (CO)
• Not stored or released in synaptic vesicles
• Made in the cell when needed
• CO & NO activate metabolites in cells (gives you
energy)
• NO also controls
• intestinal muscles
• dilates blood vessels in active sites of the brain
• dilates blood in sex organs (viagra), (but does
not produce sexual arousal)
• Neurotransmitters
• Synthesis of SMT
• Amines
• Tyrosine from diet (e.g., hard
cheese, bananas..)
• Converted (tyrosine hydroxylase
enzyme) into L-dopa, then into DA,
NE, EP
• Supply of DA, NE, and EP are directly
related to supply of tyrosine
hydroxylase regardless of how much
tyrosine is in your system
• Neurotransmitters
• Synthesis
• Peptide transmitters (Large molecules)
• Over 50 amino acid chains for the PT family
• Most are synthesized in mRNA
• Assembled in ribosome & packaged in Golgi bodies
• Transported in microtubles to terminal buttons
• Family: Opiods, Neurohypophyseals, Secretins,
Insulins, Gastrins, Somatostatins, Corticosteroids
• Neurotransmitters
• Synthesis
• Peptide transmitters
(Large molecules)
• PT transmitters do not
bind to ion channels
• No direct effects
on voltage-gated
membrane
functions
• PT activate synaptic
receptors that
indirectly influence cell
structure and function
• Agonistic Drug (Enhance)
• Drug
• Binds to autoreceptors on
presynaptic membrane
• Blocks inhibitory effect on
neurotransmitter release
• Binds to postsynaptic
receptors
• Activate receptors OR
• Increase neurotransmitter
effect
• Blocks deactivation of
neurotransmitter on
postsynaptic membrane
• I.E., blocks degradation or re-
uptake
• Antagonistic Drugs (Block)
• Drug
• Blocks synthesis of
neurotransmitter
• Cause vesicles to leak and
neurotransmitters are
destroyed by degradation
• Blocks release of
neurotransmitter from terminal
buttons
