Lecture 2: Membrane Potentials - Synapses - Neurotransmitters Flashcards
Besides neurons, what other cell have the capacity to generate electricity?
muscle cells
What is a specific feature of neurons?
Their capacity to generate electricity
Neurons have ___ that allow them to ___
Neurons have high density of ions channels on their plasma
membrane that allow them to control the flow of different ions
and thus generate electrical potentials (i.e. potential difference).
Neurons generate _
Electrical potentials (signals) to transmit information throughout the brain and the body
What are the four types of membrane potentials:
(1) Resting membrane potential (Vm)
(2) Action potential
(3) Receptor potential
(4) synaptic potential
Resting membrane potential (Vm):
- At resting state (in absence of stimulus).
-Results from a polarization of the plasma membrane (potential difference)
- Always negative (~ -90 to -70 mv).
Resting membrane potential (Vm) results from:
polarization of the plasma membrane (potential difference)
Action potential:
- Results from transient changes in the
membrane potential of a stimulated neuron - Electrical signal that travels along axons.
- Long range transmission of information within
the nervous system.
Action potential results from:
Transient changes in the
membrane potential of a stimulated neuron.
Receptor potential results from:
Transient changes in the
membrane potential of a receptor of sensory neurons by external stimuli
Synaptic potential results from:
the communication of signals between neurons at the synaptic contact.
Synaptic potential is recorded at:
The post-synaptic neuron by the stimulation of the pre-synaptic neuron.
At rest, the neuron is __
polarized
At rest, the neuron is polarized, what does polarized mean?
The inside of the cell is more negative than the outside
The voltage of the resting membrane potential (Vm) is typically:
-70 to -90 mV
The resting membrane potential is caused by:
a difference in the concentration of ions inside and outside the cell
At the resting state, ALL voltage-gated sodium channels (Na+) and MOST voltage-gated potassium (K+) channels are:
closed
The Na+/K+ pump transports more __ ions out than __ inside the cell, keeping the inside more __
The Na+/+ pump transports more Na+ ions out than K+ inside the cell, keeping the inside more negative
The intracellular fluid is filled with
negatively charged proteins
An action potential (AP) is a:
very rapid shift (milliseconds) in the membrane potential from “-“ to “+” values and return back to initial resting potential level “-“
What are the three phases of the action potential ?
(1) Depolarization phase (from “-“ to “+”)
(2) Repolarization phase (back to “-“)
(3) Hyperpolarization phase (below “Vm” aka resting membrane potential)
The 3 phases of the AP are caused by the activation of:
Two special types of ion channels on the nerve membrane:
(1) voltage-gated Na+ channels
(2) voltage-gated K+channels
In the depolarization phase, the initial increase in membrane potential can be caused by:
Mechanical, electrical, or chemical stimulation
Describe the depolarization phase in 7 steps:
(1) Initial increase in membrane potential (can be caused by mechanical, electrical or chemical stimulation)
(2) If the membrane potential rises, some voltage-gated Na+ channels start to open
(3) Na+ ions flow inside (more positivity inside the cell)
(4) The potential rises, further to reach a threshold level (about 65 mV)
(5) Causes more and more Na+ channels to open one after another
(6) It creates a positive-feedback cycle (i.e. domino effect)
(7) The potential reaches the overshoot level (above 0 mV)
The repolarization phase is characterized by:
Return back of the membrane potential toward the resting potential (i.e. back to the “-“ level)
The repolarization phase is caused by:
The activation of K+ channels and deactivation of Na+ channels
K+ channels are activated when:
Membrane potential increases above 0 mV (overshoot)
K+ gates open __ at the same time when __
K+ gates open slowly at the same time when Na+ channels begin to close
In the repolarization phase, K+ ions flow __
outside
In the repolarization phase, Na+ ions are __
blocked from flowing
back inside
During the repolarization phase of action potential the inside is more _ than the outside
During the repolarization phase of the action potential the inside is more negative(only negative proteins) than the outside
during the repolarization phase of the action potential, the membrane potential __
returns toward the resting state level (-90mV)
During the hyperpolarization phase:
-K+ channel gates remain open for a few milliseconds after repolarization phase is completed: excess K+ flow out of cell (inside more negative) –> membrane potential goes more negative than Vm (hyperpolarization)
- Back to resting stage: K+ channel gates close and membran potential comes back to its resting stage (-70mV)
The threshold of an action potential is:
the level of membrane potential at which Na+ channels start to open one after another in a positive-feedback cycle
The threshold of an AP is preceded by :
a sub-threshold potential (no AP yet)
The threshold of an action potential occurs when:
The number of Na+ ions entering the neuron becomes greater than the number of K+ ions leaving the neuron
- about -55 mv (for a neuron with Vm = -70 mV)
- about -65 mv (for a neuron with Vm = -90 mV)
all or none principle of action potentials?
AP is said to be all-or-none signal, since either it occurs fully or it
does not occur at all (i.e. there is no ½AP or ¼AP, there is 1AP).
If the threshold level is reached , __
the AP occurs
The amplitude (voltage) of an AP is ___ of the intensity of the stimulus that evokes it
The amplitude (voltage) of an AP is NOT DEPENDENT of the intensity of the stimulus that evokes it
The frequency of firing (number of APs) is __ on the intensity of the stimulus
DEPENDENT
AP propagates along:
Neuronal axons and fibers
AP excites :
adjacent portions of the membrane, resulting in propagation of the AP
What does the Na+ ion flow to adjacent areas do in propagation of Action Potential - Unmyelinated Nerve Fibers:
-open more voltage-gated Na+ channels
-increase voltage of adjacent area to reach threshold level
-initiate a new AP in the adjacent area
The adjacent propagation of AP occurs in :
unmyelinated axon (axons not covered by a myelin sheath)
What is the conduction velocity of adjacent propagation
conduction velocity (speed) is slow = 0.25m/s
In the myelinated nerve fiber (axon), the axon is surrounded by:
myelin sheath (fatty white substance)
the myelin forms:
wrapping layers around the axon
Myelin is produced as an extension of:
the glial cells
–>either Schwann cells in the peripheral nervous system
–>oligodendrocytes in the central nervous system
Schwann cells produce:
Myelin in the peripheral nervous system
Oligodendrocytes produce :
myelin in the central nervous system
About once every 1- 3 mm, myelin sheath is interrupted by:
a node of Ranvier
Ions canot flow significantly through:
Thick myelin sheath, which insulates nerve fiber
Saltatory conduction:
Action potential can only occur at the nodes of Ranvier (where voltage-gated channels are located) and is conducted from node to node
Saltatory conduction results in:
Fast conduction
Increases 5 to 50 folds –> 100m/s
Saltatory conduction conserves:
energy for axon (little metabolism required to activate ion channels)
Propagation of action potential : conduction velocity: unmyelinated vs myelinated
Unmyelinated: 0.25 m/s
Myelinated: 100m/s
Initial point of generation of AP:
Ap do not begin near soma & dendrites but rather at the intial segment of the axon called AXON HILLOCK
Direction of propagation:
AP travels from the axon hillock toward the synaptic terminal of the axon (no reverse direction)
What are the three main functions of action potentials?
(1) Transmitting information
(2) Encoding information (neuronal language)
(3) Rapid transmission over distance (< second)
What are the three ways in which action potential transmit information?
(1) Transfer all sensory information from the periphery to the central nervous system (CNS)
(2) Transfer all motor information from CNS to periphery (e.g. muscles, joint, etc)
(3) Transfer information between different parts of CNS
How do action potentials encode information (neuronal language)
Encoding information in the form of APs
The frequency of APs (number APs) defines the code
Action potentials enable rapid transmission over distances, speed of transmission depends on:
Fiber size and whether the axon is myelinated or not
Multiple Sclerosis (MS) is :
An immune-mediated inflammatory disease that causes the demyelination of neuronal fibers in the central nervous system
MS symptoms:
Progressive muscle weakness
Loss of sensation
Loss of vision
Death
Demyelination causes
The blockage
in the conduction (propagation) of AP
All-or-none principle:
If conditions are not right
→ “Stop” AP propagation
Information is transmitted within the neuron by
action potential (electrical signal)
Information is communicated between neurons through:
synapse
(point of communication between two neurons).
synapse is the contact point between:
Two neurons
Pre-synaptic neuron
(sending neuron)
Post-synaptic neuron
(receiving neuron)
The space between the pre- and post-
synaptic neurons is called
the synaptic
cleft (200 - 300 angstrom = 20nM-30nM)
Synapses in the human brain fall into
two classes:
Electrical synapses (electrical signal)
➢ Chemical synapses (chemical signal)
These two classes of synapses can be
distinguished based on
Their structures
and the mechanisms they use to
transmit signals from the presynaptic
to the postsynaptic element.
Electrical synapses permit
direct,
passive flow of electrical current from
one neuron to another.
Electrical current (ions) flow through
intercellular continuities called
connexons (channel bridges).
connexons are grouped in small areas
called
gap junctions.
transmission in electrical synapses is :
very fast because the current flow across connexons is virtually instantaneous
electrical transmission can be:
bidirectional,allowing electrical synapses to
synchronize electrical activity among
populations of neurons.
Electrical synapses are __ and are
mostly ___ synapses.
Electrical synapses are minority and are
mostly inhibitory synapses.
At chemical synapses, there are
no
connexons (no intercellular continuity)
between the two neurons (synaptic cleft
= empty space).
At the Presynaptic terminal, there are
synaptic vesicles containing chemical
substances called
‘Neurotransmitters’.
Synaptic transmission is initiated when :
an AP invades the presynaptic
terminal and causes the release of
neurotransmitters into the synaptic
cleft.
The binding of neurotransmitters
into the postsynaptic receptors
causes
the activation of the
postsynaptic receptors and thus a
change in the membrane potential.
Neurotransmitter also called
ligand
Neurotransmitter is a chemical substance that:
is synthetized and packaged in the
presynaptic terminal, and released into the synaptic cleft by the arrival of a nerve
impulse (AP).
By binding to its specific receptor, the neurotransmitter causes:
the transfer of the impulse to the postsynaptic neuron
types of neurotransmitters is based on:
the action on
the postsynaptic neuron
excitatory neurotransmitters:
Excite (depolarize) postsynaptic
membrane (i.e. more likely to generate AP)
What are some examples of excitatory neurotransmitters?
-Glutamate
-Dopamine
-Acetylcholine
-Serotonin
-Norepinephrine
Inhibitory neurotransmitters:
Inhibit (hyperpolarize) postsynaptic
membrane (i.e. less likely to generate AP):
what are some examples of inhibitory neurotransmitters?
GABA
GLYCINE
Glutamate
Excitatory
Dopamine
Excitatory
Acetylcholine
Excitatory
Serotonin
Excitatory
Norepinephrine
Excitatory
GABA
Inhibitory
Glycine
Inhibitory
Each neurotransmitter has
his specific postsynaptic
receptor (e.g. key and lock).
Examples of small molecule, rapidly acting transmitters
Glutamate (Glu)
GABA,
Glycine
Dopamine (DA)
Norepinephrine (NE)
Acetylcholine (ACh)
Serotonin (5HT)
Nitritc oxide
large molecule, __ transmitter = neuropeptides
large molecule, slow actinf transmitters, neuropeptides
What are some examples of large molcule, slow acting transmitters, neuropeptides(4)?
Hypothalamic-releasing hormones
Pituitary peptides
Peptides that act on gut and brain
Peptides from other tissues
Two types of postsynaptic receptors:
➢ Ionotropic receptors
➢ Metabotropic receptors
The two types of postsynaptic receptors contain 2 components:
(1) A binding component which binds to the neurotransmitter
(2) An active component (activated by binding of the neurotransmitter) * this part is different depending on the type of receptor
In ionotropic receptors, the active component is:
an ion channel
In metabotropic receptors, the active component is:
a second messenger activator (G-protein)
In the ionotropic receptors, the ion channel (active component) is an
__ of the receptor. Once the neurotransmitter binds into the
receptor, the ion channel is __.
In the ionotropic receptors, the ion channel (active component) is an
integrated part of the receptor. Once the neurotransmitter binds into the
receptor, the ion channel is activated.
Two types of ion channels:
(1) cation channels
(2) anion channels
Cation channels
allow cations (+ ions) (e.g. Na+, Ca2+, K+) to pass. These
channels excite (depolarize) the postsynaptic neuron. Make inside the cell
positively charged (e.g. Glutamate receptor).
Anion channels:
allow anions (- ions)(e.g. Cl-) to pass. These channels
inhibit (hyperpolarize) the postsynaptic neuron. Make inside the cell
negatively charged (e.g. GABA receptor
The ionotropic receptors open and closes rapidly (< sec) providing __
The ionotropic receptors open and closes rapidly (< sec) providing a very
rapid control of postsynaptic neurons: fast synaptic transmission.
In the Metabotropic Receptor, the active component is
not an
integrated part of the receptor
In the Metabotropic Receptor, the active component is not an
integrated part of the receptor. It is a
protein structure “second
messenger activator’’ that causes prolonged changes in the
neurons (minutes to months) by activating substances inside the
postsynaptic neuron, slow synaptic transmission.
metabotropic receptors have __ synaptic transmission
slow
ionotropic receptors have __ synaptic transmission
fast
The most common type of second
messenger activator uses
G-proteins as
an active component:
The G-protein is a
protein complex (α,
β, γ sub-units) attached to the interior
portion of binding component.
The binding of the neurotransmitter on
the metabotropic receptor activates:
the G-protein,
which initiates a cascade of events
leading to alterations in the cellular
activity.
Upon the activation of the G-protein complex, the α sub-unit
detaches from
the complex and activates multiple functions inside the cell (e.g. opens ion channels, activates membrane enzymes, activates intracellular enzymes,
activates gene transcription).
in metabotropic receptors, Slow synaptic transmission: causes
prolonged changes in the neurons (up
to months).
The binding of the neurotransmitter on the post-synaptic receptor
(ionotropic receptors)
opens ions channels and increases the permeability of ions
The binding of the neurotransmitter on the post-synaptic receptor
(ionotropic receptors) opens ions channels and increases the permeability of ions, causes
the postsynaptic membrane potential to shift from the resting state
(Vm). The new potential is called postsynaptic potential (PSP)
Excitatory postsynaptic potential (EPSP):
The membrane potential moves towards less negative
values (> Vm, depolarization).
Excitatory postsynaptic potential (EPSP):Increased permeability to
Na+ and/or Ca2+ (more
positivity inside).
Excitatory postsynaptic potential (EPSP)Caused by the activation of
excitatory receptors.
EPSP favours:
the generation of AP (depolarized
membrane)
Inhibitory postsynaptic potential (IPSP):
The membrane potential moves towards more negative
values (< Vm, hyperpolarization).
Inhibitory postsynaptic potential (IPSP):Increased permeability to
Cl- and/or K+ (more Negativity
inside
Inhibitory postsynaptic potential (IPSP), caused by the activation of :
inhibitory receptors.
IPSP ___ the generation of AP (hyperpolarized
membrane).
IPSP blocks the generation of AP (hyperpolarized
membrane).
Characteristics of postsynaptic potentials (5) :
(1)Sub-threshold potentials (below threshold of AP)
(2) Do not obey to the All-or-none principle (i.e. more stimulus,
higher the amplitude).
(3)EPSP favorites the generation of AP (signal transmission)
(4) IPSP blocks the generation of AP (no signal transmission)
(5)Summation of different PSPs (Spatial & Temporal).
Spatial Summation:
when different
presynaptic terminals (E1 & E2)
stimulate the same postsynaptic
neuron, their respective EPSPs summate
(i.e. superpose)
If the postsynaptic neuron receives an
excitatory stimulus (E1) and an
inhibitory stimulus (I), the 2 stimuli
cancel each other
Temporal Summation:
when a
postsynaptic neuron receives, in a very
short period of time, successive
stimulations, form the same
presynaptic terminal (e.g. E1), the 2nd
EPSP will generate before the recovery of
the 1st one, thus both EPSPs can
summate.
Rapid successive discharges from the
same presynaptic terminal can
summate
to reach the threshold for firing AP
Synaptic plasticity is the ability of a synapse to
change (strengthen or weaken) over time, in
response to increase or decrease in its activity
Synaptic plasticity results from (3):
- Change in the quantity of neurotransmitters released
- Change in the number of postsynaptic receptors,
- Change in the response of the postsynaptic neuron to presynaptic stimulation (EPSP & IPSP).
What are the four types of synaptic plasticity:
(1) synaptic potentiation (enhancement)
(2) synaptic depression
(3) short term plasticity
(4) long term plasticity
Synaptic potentiation (enhancement)
Increase in
the efficacy of the synapse
Synaptic depression:
Decrease in the efficacy of the
synapse.
Short-term plasticity:
lasts from few milliseconds to
minutes
Long-term plasticity:
lasts from minutes to months
(even years).
Synaptic plasticity is an important neurochemical
mechanism of
learning and memory (Hebbian theory:
“cells that fire together, wire together”).
Effect of Ecstasy on Serotonin transmission:
In a healthy brain, serotonin is rapidly reuptaked from synaptic cleft by the Reuptake Transporter.
In the presence of Ecstasy, the later blocks the
job of the Reuptake Transporter,
Serotonin sties longer in the synapse and over
stimulates the postsynaptic neuron.
Ecstasy causes
euphoric sensation, increased
heart rate, panic attacks, blurred vision, nausea,
vomiting, convulsions and death (overdose).
