Week 3: Neuronal Communication & Chemical Messengers Flashcards
Sequence of neural communication (between 2 neurons)
- From Resting Membrane
Potential to generating
The Action Potential (in
neuron A) - Release of
neurotransmitters into
the synaptic cleft - Binding to the post-synaptic neuron to
change resting
membrane potential (in
neuron B)
Membrane potential
The electrical charge across a cell membrane (voltage unit = mV)
* the difference in electrical potential inside the cell, relative to outside, which is zero.
Resting membrane potential
The potential of a neuron when it is not being altered by excitatory or inhibitory innervation;
* Voltage is more negative inside relative to outside; -40 to -90 mV (-70mV)
Ions
Charged molecules
◦ Cations (K+, Na+, Ca2+) & Anions (Cl-)
How is resting membrane potential disturbed?
By depolarizing (+) or hyperpolarizing (-) the cell
Diffusion
Movement of molecules from regions of high concentration to regions of low concentration (Along the Concentration Gradient)
Electrostatic Pressure
Opposites attract; Similarity repulse = Electrical
Gradient (polarization)
Two ways Polarization (Electrical Gradient) is maintained:
- Voltage-gated ion channel
- Sodium-Potassium pump
Voltage-gated Ion channel
An integral protein along the cell membrane that opens or closes according to the value of the membrane potential
* At rest: Na+ is closed; concentration greater outside cell than inside cell
* At rest: K+ is closed; concentration greater inside cell than outside cell
Sodium-Potassium pump (Active transport pump)
A transmembrane protein that transports ions against their concentration gradient
* Pushes 3 Na+ out of the cell and draws 2 K+ into cell
* Requires energy (ATP) (active transport)
* Role: Regulate ion concentrations
* Result: Na+ is 10x more concentrated outside cell than inside
Role of Concentration gradient (diffusion) and Electrical gradient (electrostatic pressure) in generating an AP from RMP:
- Both act on Na+ to enter the cell
- Diffusion forces K+ out of the cell while electrostatic pressure forces K+ into the cell
- Leaky K+ channel (Net movement: greater concentration inside cell)
Action Potential
Electrical charge that runs down the axon from the axon hillock to the terminal buttons.
It is a brief electrical signal that provides the basis for conduction of information along an axon
3 phases to an action Potential:
Depolarization
Repolarization
Hyperpolarization
Depolarization
Reduction (toward zero) of the
membrane potential of a cell from its normal
resting potential. Intracellular space becomes more
positive
Repolarization
Increase in the membrane
potential of a cell toward resting. Intracellular
space becomes more negative once more
Hyperpolarization
An increase in the membrane
potential of a cell, relative to the normal resting
potential. Overshoot of RMP
Threshold of Excitation
-All-or-none action potential
- The level that a depolarization must reach for an action potential to occur. In most neurons the threshold is around -55mV to -65mV.
2 Principles for conduction of the action potential:
- All-or-none Law
- Rate Law
All-or-none Law
The principle that once an action potential is triggered in an axon, it is propagated without growing or diminishing to the end of the fiber (terminal buttons).
Rate Law
The principle that variations in the intensity of a stimulus or other information being transmitted along an axon are represented by variations in the rate at which that axon fires (i.e., number of APs).
The strength of the information is determined by frequency of the AP being generated along the axon, not the magnitude of the AP.
Propagation of the Action Potential Facilitated by Myelin means…
Less time and energy required
From RMP to AP Steps:
- Threshold of excitation reached
- Action potential generated at axon hillock
- Signal moves down axon (non-decrementing)
- Signal reaches terminal buttons
Sherrington’s Properties of the Synapse:
- Reflexes are slower than conduction along an axon.
- Several weak stimuli presented at slightly different times or locations produce a stronger reflex than a single stimulus does.
- When one set of muscles become excited, a different set becomes relaxed.
Temporal Summation:
combined effect of repeated stimulation at a single
synapse onto one neuron.
Spatial summation:
combined effect of several nearly simultaneous
stimulations at several synapses onto one neuron
Presynaptic membrane
The membrane of a terminal button that lies
opposite to the postsynaptic membrane, through which the neurotransmitter is released
Postsynaptic membrane
The cell membrane opposite the terminal button
in a synapse, receives the message.
Synaptic cleft
The space between the presynaptic and postsynaptic membrane
Synaptic vesicle
A small, spherical hollow organelle; contain molecules of a neurotransmitter.
Release zone
Interior of the presynaptic membrane to which vesicles attach and release their neurotransmitter into the synaptic cleft.
Postsynaptic density
portion of postsynaptic membrane where receptors are located for binding.
3 types of synapses:
- Axodendritic
- Axosomatic
- Axoaxonic
Axodendritic synapses
located on the smooth surface of a dendrite or
on dendritic spines
Axosomatic synapses
located on somatic membrane
Axoaxonic synapses
consist of synapses between two terminal
buttons.
Does not contribute to neural integration
Controls amount of chemical release by post-synaptic axon terminals
Presynaptic inhibition
reduces the amount of neurotransmitter released by the postsynaptic terminal button.
Presynaptic facilitation
increases the amount of neurotransmitter released by the postsynaptic terminal button.
Steps for communication at the Synapse
- Synthesis and Release of neurotransmitter from
presynaptic terminals - Binding and Activation of postsynaptic receptors
- Postsynaptic potential (EPSP or IPSP)
- Termination of postsynaptic potential
- Synthesis and release of Neurotransmitters
▪NT are Synthesized in soma/terminal buttons
▪ Calcium channels open
▪ Synaptic vesicle fuses with membrane (Exocytosis)
▪ Vesicles break open and release neurotransmitters into the synaptic cleft
Postsynaptic receptor
A receptor in the postsynaptic membrane of a
synapse that contains a binding site for a neurotransmitter (ligand)
Neurotransmitter-dependent ion channel (ligand-gated)
An ion channel that opens when a molecule of a neurotransmitter binds with a postsynaptic receptor.
Ionotropic receptor
A receptor that contains a binding site for a neurotransmitter and an ion channel that opens when the neurotransmitter attaches to the binding
site. Fast acting (ligand-gated channel)
Metabotropic receptor
A receptor that contains a binding site for a neurotransmitter which then activates an enzyme that begins a series of events that opens an ion
channel elsewhere in the membrane of the cell. Slow but amplified (G-protein-coupled receptors)
- Binding and Activation of Postsynaptic Receptors
▪2 ways that neurotransmitters open ion channels of postsynaptic cell: Ionotropic receptor & Metabotropic receptor
Ionotropic receptor (aka: ligand-gated channels): receptor with binding and ion channel
* The ion channel opens when a ligand/ neurotransmitter attaches to the binding site.
* Fast acting post-synaptic effects
Metabotropic receptor (aka: g-protein coupled
receptors): receptor with binding site but no ion
channel
◦ Binding leads to activation of intermediate proteins
called G-protein
◦ G-protein influences opening of ion channels
elsewhere along the cell membrane
◦ G-protein may also influence enzymes and activate
intracellular signaling molecules called second
messengers
◦ Slow but long lasting
- Postsynaptic Potential (Excitatory/Inhibitory)
- Depends on the ion channels that the receptor opens.
- 3 major types neurotransmitter-dependent ion channels:
- Sodium (Na+) = excitatory
- Potassium (K+) = inhibitory
- Chloride (Cl-) = inhibitory
Excitatory postsynaptic potential
- An excitatory depolarization of the postsynaptic membrane of a synapse.
- Increase Na+ into the cell
- increases chances of cell reaching Threshold of excitation
Inhibitory postsynaptic potential
- An inhibitory hyperpolarization of the postsynaptic
membrane of a synapse. - Increase flow K+ out or Cl- into the cell
- Decrease chances of reaching threshold of excitation
Neural integration
The process by which inhibitory and excitatory postsynaptic potentials summate and control the rate of firing of a neuron.
- Termination of Postsynaptic Potential
Reuptake and Enzymatic deactivation
Reuptake
The reentry of a NT just released by a terminal button back through its membrane.
▪ Specialized transporter proteins (e.g., 5HT transporter)
Enzymatic deactivation
The destruction of a NT by an enzyme after its release.
▪ Specialized enzyme proteins (e.g., Acetylcholinesterase (Ache), Monoamine Oxidase (MAO)
Non-chemical Communication Between neurons
*Electrical transmission via Gap Junctions
*Ion channels are always opened and
aligned between 2 cells
*Faster transmission than chemical
synapse
*More abundant during neural
development
Neurotransmitter criteria:
▪Chemicals produced within a neuron
▪Released by a neuron following depolarization and binds to receptors on adjacent post-synaptic neuron
▪Exogenous administration mimics endogenous release (i.e., drugs)
▪Does not remain in the synaptic cleft for a long period (clearance via reuptake or deactivation)
Neuromodulators/Neuropeptides
▪Not restricted to the synaptic cleft and diffuses through the extracellular
fluid, traveling further and more widely dispersed.
▪ E.g., Dopamine, Serotonin, Acetylcholine
Hormones
▪A chemical substance that is released by an endocrine gland into the blood
that binds to target cells in other organs (and in the brain).
▪ E.g., Cortisol, Insulin, Leptin
Types of Neurotransmitters
- Amino acids: glutamate, GABA, glycine
- Acetylcholine (Ach)
- Monoamines: serotonin (5HT), dopamine (DA), NE, E
- Neuropeptides: endorphins, neuropeptide Y
- Purines: adenosine
- Gases: nitric oxide (NO)
Amino acids
- Glutamate - excitatory; implicated in cognitive functioning
- GABA - inhibitory NT in the brain
- Glycine - inhibitory role in spinal cord, brain stem and retina.
Acetylcholine
- PSP depends on the receptor: nicotinic (excitatory); muscarinic (inhibitory or excitatory)
- The primary NT secreted by the efferent axons of the CNS
- Implicated in Alzheimer’s disease: 90% drop in Ach (AChe Inhibitors as TX)
Indolamine -Serotonin
▪ Made from Tryptophan (amino acid)
▪ Important for mood, eating, sleep, arousal, pain, dreaming
▪ Drugs that perturb 5HT: Ecstasy, LSD, SSRIs
Catecholamines - Dopamine - Norepinephrine-Epinephrine
▪ Made from Tyrosine (amino acid)
▪ DA: Important for movement, learning, motivation, compulsion, emotion, sexual behaviour =
basic motivational behaviours
▪ 3 main dopaminergic systems: Mesolimbic, Nigrostriatal, Mesocortical DA system
DA Systems
- Degeneration of Nigrostriatal
pathway implicated in Parkinson’s
Disease - Dysregulated Mesolimbic (high) and
Mesocortical (low) pathway
implicated in Schizophrenia - Dysregulated Mesocortical (low)
and Nigrostriatal (high) pathway in
ADHD.
