Chapter 4Neural Conduction and Synaptic TransmissionHow Neurons Send and
Receive Signals
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The Neuron’s Resting Membrane Potential
Inside of the neuron is negative with respect to the outside
Resting membrane potential is about -70mV
Membrane is polarized, it carries a charge
Why?
Ionic Basis of the Resting Potential
Ions, charged particles, are unevenly distributed
Factors influencing ion distribution• Homogenizing
• Factors contributing to uneven distribution
Ionic Basis of the Resting Potential
Homogenizing• Random motion – particles tend to move down
their concentration gradient
• Electrostatic pressure – like repels like, opposites attract
Factors contributing to uneven distribution• Membrane is selectively permeable
• Sodium-potassium pumps
Ions Contributing to Resting Potential
Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-)
• synthesized within the neuron
• found primarily within the neuron
The Neuron at Rest
Ions move in and out through ion-specific channels
K+ and Cl- pass readily Little movement of Na+ A- don’t move at all, trapped inside
Equilibrium Potential
The potential at which there is no net movement of an ion – the potential it will move to achieve when allowed to move freely
Na+ = 120mV K+ = -90mV Cl- = -70mV (same as resting potential)
The Neuron at Rest Na+ is driven in by both electrostatic forces
and its concentration gradient K+ is driven in by electrostatic forces and out
by its concentration gradient Cl- is at equilibrium Sodium-potassium pump – active force that
exchanges 3 Na+ inside for 2 K+ outside
Something to think about
What would happen if the membrane’s permeability to Na+ were increased?
What would happen if the membrane’s permeability to K+ were increased?
Generation and Conduction of Postsynaptic Potentials (PSPs)
Neurotransmitters bind at postsynaptic receptors
These chemical messengers bind and cause electrical changes• Depolarizations (making the membrane potential less
negative)
• Hyperpolarizations (making the membrane potential more negative)
Generation and Conduction of Postsynaptic Potentials (PSPs) Postsynaptic depolarizations = Excitatory
PSPs (EPSPs) Postsynaptic hyperpolarizations = Inhibitory
PSPs (IPSPs) EPSPs make it more likely a neuron will fire,
IPSPs make it less likely PSPs are graded potentials – their size varies
EPSPs and IPSPs
Travel passively from their site of origination Decremental – they get smaller as they travel 1 EPSP typically will not suffice to cause a
neuron to “fire” and release neurotransmitter – summation is needed
Integration of PSPs and Generation of Action Potentials (APs)
In order to generate an AP (or “fire”), the threshold of activation must be reached at the axon hillock
Integration of IPSPs and EPSPs must result in a potential of about -65mV in order to generate an AP
Integration
Adding or combining a number of individual signals into one overall signal
Temporal summation – integration of events happening at different times
Spatial - integration of events happening at different places
What type of summation occurs when:
One neuron fires rapidly? Multiple neurons fire at the same time? Several neurons fire repeatedly? Both temporal and spatial summation
occur simultaneously
The Action Potential
All-or-none, when threshold is reached the neuron “fires” and the action potential either occurs or it does not.
When threshold is reached, voltage-activated ion channels are opened.
The Ionic Basis of Action Potentials
When summation at the axon hillock results in the threshold of excitation (-65mV) being reached, voltage-activated Na+ channels open and sodium rushes in.
Remember, all forces were acting to move Na+ into the cell.
Membrane potential moves from -70 to +50mV.
The Ionic Basis of Action Potentials
Rising phase: Na+ moves membrane potential from -70 to +50mV.
End of rising phase: After about 1 millisec, Na+ channels close.
Change in membrane potential opens voltage-activated K+ channels.
Repolarization: Concentration gradient and change in charge leads to efflux of K+.
Hyperpolaization: Channels close slowly - K+ efflux leads to membrane potential <-70mV.
Refractory Periods
Absolute – impossible to initiate another action potential
Relative – harder to initiate another action potential
Prevent the backwards movement of APs and limit the rate of firing
The action potential in action
http://intro.bio.umb.edu/111-112/112s99Lect/neuro_anims/a_p_anim1/WW1.htm
http://bio.winona.msus.edu/berg/ANIMTNS/actpot.htm
PSPs Vs Action Potentials (APs)
EPSPs/IPSPs Decremental Fast Passive (energy is
not used)
Action Potentials Nondecremental Conducted more
slowly than PSPs Passive and active
Conduction in Myelinated Axons
Passive movement of AP within myelinated portions occurs instantly
Nodes of Ranvier (unmyelinated)• Where ion channels are found
• Where full AP is seen
• AP appears to jump from node to node• Saltatory conduction
• http://www.brainviews.com/abFiles/AniSalt.htm
Structure of Synapses
Most common• Axodendritic – axons on dendrites
• Axosomatic – axons on cell bodies Dendrodendritic – capable of
transmission in either direction Axoaxonal – may be involved in
presynaptic inhibition
Synthesis, Packaging, and Transport of Neurotransmitter (NT)
NT molecules• Small
• Synthesized in the terminal button and packaged in synaptic vesicles
• Large• Assembled in the cell body, packaged in vesicles,
and then transported to the axon terminal
Release of NT Molecules Exocytosis – the process of NT release The arrival of an AP at the terminal opens
voltage-activated Ca++ channels. The entry of Ca++ causes vesicles to fuse with
the terminal membrane and release their contents
http://www.tvdsb.on.ca/westmin/science/sbioac/homeo/synapse.htm
Activation of Receptors by NT
Released NT produces signals in postsynaptic neurons by binding to receptors.
Receptors are specific for a given NT. Ligand – a molecule that binds to another. A NT is a ligand of its receptor.
Receptors
There are multiple receptor types for a given NT.
Ionotropic receptors – associated with ligand-activated ion channels.
Metabotropic receptors – associated with signal proteins and G proteins.
Ionotropic Receptors
NT binds and an associated ion channel opens or closes, causing a PSP.
If Na+ channels are opened, for example, an EPSP occurs.
If K+ channels are opened, for example, an IPSP occurs.
Metabotropic Receptors
Effects are slower, longer-lasting, more diffuse, and more varied.
NT (1st messenger) binds > G protein subunit breaks away > ion channel opened/closed OR a 2nd messenger is synthesized > 2nd messengers may have a wide variety of effects
Reuptake, Enzymatic Degradation, and Recycling
As long as NT is in the synapse, it is active – activity must somehow be turned off.
Reuptake – scoop up and recycle NT.
Enzymatic degradation – a NT is broken down by enzymes.
Small-molecule Neurotransmitters
Amino acids – the building blocks of proteins
Monoamines – all synthesized from a single amino acid
Soluble gases Acetylcholine (ACh) – activity terminated
by enzymatic degradation
Amino Acid Neurotransmitters
Usually found at fast-acting directed synapses in the CNS
Glutamate – Most prevalent excitatory neurotransmitter in the CNS
GABA –
• synthesized from glutamate
• Most prevalent inhibitory NT in the CNS Aspartate and glycine
Monoamines
Effects tend to be diffuse Catecholamines – synthesized from tyrosine
• Dopamine
• Norepinephrine
• Epinephrine Indolamines – synthesized from tryptophan
• Serotonin
Soluble-Gases and ACh
Soluble gases – exist only briefly• Nitric oxide and carbon monoxide
• Retrograde transmission – backwards communication
Acetylcholine (Ach)• Acetyl group + choline
• Neuromuscular junction
Neuropeptides
Large molecules Example – endorphins
• “Endogenous opiates”
• Produce analgesia (pain suppression)
• Receptors were identified before the natural ligand was
Pharmacology of Synaptic Transmission
Many drugs act to alter neurotransmitter activity• Agonists – increase or facilitate activity
• Antagonists – decrease or inhibit activity
• A drug may act to alter neurotransmitter activity at any point in its “life cycle”
Agonists – 2 examples
Cocaine - catecholamine agonist• Blocks reuptake – preventing the activity of
the neurotransmitter from being “turned off” Benzodiazepines - GABA agonists
• Binds to the GABA molecule and increases the binding of GABA
Antagonists – 2 examples Atropine – ACh antagonist
• Binds and blocks muscarinic receptors
• Many of these metabotropic receptors are in the brain
• High doses disrupt memory Curare - ACh antagonist
• Bind and blocks nicotinic receptors, the ionotropic receptors at the neuromuscular junction
• Causes paralysis