Resting membrane potential ~ -70mV
- Membrane is polarized
(ie) Electrical charge on the outside of the membrane is
positive while the electrical charge on the inside of the
membrane is negative
Changes in membrane potential: Terminology
Depolarization: Inside of cell becomes less negative
relative to outside (> –70 mV)
Repolarization: Membrane returns to the resting
potential (–70 mV) after depolarization
Hyperpolarization: Inside of cell becomes more
negative relative to outside (< –70 mV)
Graded potentials: Localized changes in membrane
potential (either depolarization or hyperpolarization)
- (eg) A change in membrane potential from -70 to -60mV
= a 10 mV graded potential
Action potentials: Rapid, substantial depolarization of
the membrane (–70 mV to +30 mV to –70 mV all in 1 ms)
- Signal over long distances
The Structure of a Neuron
Nerve impulse
is generated here
Direction of Impulse
Nerve Impulse: An electrical charge that passes from one neuron
to the next,and finally to an end organ, such as a group of muscle fibers
Resting state
RESTING STATE
An action potential
Serve as electrical signals in excitable tissues
Action potential
Starts as a graded potential (Small localised change in membrane potential)
Requires depolarization greater than the threshold value: 15-20 mV
Once threshold is met or exceeded, the all-or-none principle applies
The strength of stimulus is not coded by the amplitude of the AP, but
by the frequency.
- When a greater stimulus strength is applied to a neuron identical AP’s are produced more frequently.
Action potential
Overshoot
All AP’s are of the same
duration (~ 2 mSec) and
amplitude (~ -70 to +30 mV)
Hyperpolarization
Starts as a graded potential (Small localised change in membrane potential)
Requires depolarization greater than the threshold value: 15-20 mV
Once threshold is met or exceeded, the all-or-none principle applies
The strength of stimulus is not coded by the amplitude of the AP, but
by the frequency.
- When a greater stimulus strength is applied to a neuron identical AP’s are produced more frequently.
Action potential – The role of ion channels
Refractory period
• As stimulus intensity increases, the frequency of
AP’s increase
 Time between successive AP’s is reduced
 Another AP can not be produced until the preceding one has
finished
 Refractory period: Time during which the patch of axon
membrane is unable to produce another AP
Value of the refractory period?
- Allows propagation of action potential
The Velocity of an Action Potential
Effect of myelination
 Action potential is faster in myelinated fibers
Effect of neuron diameter
 Larger diameter neurons conduct nerve impulses faster
 Larger diameter neurons present less resistance to current flow
Conduction of action potentials in unmyelinated axons
- Contiguous conduction
Conduction speed: Nerve impulse travels 1 meter in 0.1s (100ms)
= 10 meters/second
Neurons have cable properties
•
This means that neurons can transmit charges
through its cytoplasm ~ 1-2mm
•
However these cable properties are poor – Why ?
1.
2.
There is high internal resistance to the spread of charges
Many charges leak out of the axon membrane
Myelinated axon
•
Myelin sheath acts as insulation
–
Prevents flux of ions across the membrane
•
Nodes of Ranvier: Interruptions in the myelin sheath (~1mm
apart)
•
Ion channels are concentrated at the nodes of Ranvier
–
•
This is where the AP’s occur
Cable properties mean the AP’s jump from node to node
–
–
Saltatory conduction
Conduction is faster in myelinated than unmyelinated axons
Conduction of action potentials in myelinated axons
- Saltatory conduction
Conduction speed: Nerve impulse travels 1 meter in 0.007s (7ms)
= 143 meters/second (14 times faster than in unmyelinated axon)
Multiple sclerosis is an autoimmune demyleinating disease of the CNS
Myelin sheath
Degradation of myelin sheath in
multiple sclerosis
Nerve cell
MRI scan showing lesions
in MS brain
Muscle
T-cells, macrophages & B-cells infiltrate
the CNS and attack the myelin sheeth
resulting in demyelination
Dysregulated conduction in a demyelinated nerve fibres in multiple sclerosis
Normal
Multiple
Sclerosis
Symptoms of MS:
- Blurred vision
- Muscle weakness
- Ataxia
Consequence of demyelination in MS
- Loss of axonal conduction for neurons of the CNS
and in clinical disability
The Synapse
 Synapse: Site of functional connection between a neuron
and another cell
CNS: Another neuron
PNS: Another neuron or an effector cell in a muscle or gland
Synapses
 Point of communication
between neurones
 Most synapses involve
neurotransmitters
 Synapses can be:
Excitatory
 Inhibitory
The two types of postsynaptic potentials are:
EPSP: Excitatory postsynaptic potentials
IPSP: Inhibitory postsynaptic potentials
Glutamate generates an excitatory
post-synaptic potential (EPSP)
EAA (Glutamate)
Ca++
EAA
Glutamate (NMDA) receptor
is a ligand-gated Ca2+ channel
+
+
+
+
+ +
GABA generates an inhibitory
post-synaptic potential
MILLIVOLTS
-50
-60
GABA
THRESHOLD
-70
Cl-
-80
GABA
TIME
GABAA receptor is a
ligand-gated Cl- channel
- -
Excitatory Postsynaptic potentials (EPSPs)
• EPSPs are graded potentials that can initiate
an action potential in an axon
• EPSPs bring the RMP closer to threshold and
therefore closer to an action potential
Inhibitory synapses and IPSPs
• Neurotransmitter binding to a receptor at
inhibitory synapses:
– Causes the membrane to become more
permeable to potassium and chloride ions
• Leaves the charge on the inner surface more
negative (due to flow of K+ out of the cell and the
flow of Cl- in)
– IPSPs bring the RMP further away from the
threshold
• Thereby reducing the postsynaptic neuron’s ability
to produce an action potential
Summation
• A single EPSP cannot induce an action potential
• EPSPs must summate temporally or spatially to
induce an action potential
• Temporal summation
– One pre-synaptic neuron transmits impulses in rapidfire order
• Spatial summation
– Postsynaptic neuron is stimulated by a large number
of pre-synaptic neurons at the same time
• IPSPs can also summate with EPSPs, canceling each
other out
Recording electrode
Recording electrode
Integration of EPSPs and IPSPs occurs here
Key steps in chemical neurotransmission
1. Synthesis
2. Storage
3. Release
Pre-synaptic neuron
• Action potential
• Ca2+ influx
• NT release (Exocytosis)
4. Receptor binding & activation
–
Generation of a postsynaptic potential
5. Inactivation
–
Metabolism/Reuptake
Post-synaptic neuron
What happens on the pre-synaptic side ?
• AP arrives at the nerve terminal
• Nerve terminal membrane is depolarized
• Depolarization causes voltage regulated Ca2+ channels to open
• Ca2+ influx
Action potential
Ca2+
Ca2+
[Ca2+]i = 100 nM
[Ca 2+]e = 1-2 mM (10,000 fold difference approx.)
⇨ Ca2+ enters the nerve terminal down the concentration gradient
What happens on the pre-synaptic side ?
• Ca2+ activates enzymes and proteins in the nerve terminal
• Synaptic vesicles fuse with the plasma membrane & release
their contents into the synaptic cleft by exocytosis
Action potential
Ca2+
Ca2+
There is a time delay of 0.5ms in synaptic transmission
⇨ Time needed for Ca2+ to enter & cause exocytosis of transmitter
Neurotransmitters
• Amines: Catecholamines, Acetylcholine, Serotonin
• Amino acids: Glutamate, GABA and Glycine
• Neuropeptides
Action potential
Generate
EPSP
or
IPSP
Ca2+
Ca2+
Neurotransmitters can be either exicitatory or inhibitory
- Amount of neurotransmitter released is proportional to the
frequency of action potentials produced at the nerve terminal
Summary: The Nerve Impulse
 A neuron's RMP of –70 mV is maintained by the sodiumpotassium pump.
 Changes in membrane potential occur when ion channels
open, permitting ions to move from one side of the
membrane to the other.
 If the membrane potential depolarizes by 15 to 20 mV
the threshold is reached, resulting in an action potential.
 Impulses travel faster in myelinated axons and in neurons
with larger diameters.
 Saltatory conduction refers to an impulse traveling along a
myelinated fiber by jumping from one node of Ranvier to
the next.
 Action potential results neurotransmitter release
 The neurotransmitter can generate an IPSP or EPSP in the
post-synaptic neuron