Transcript Chapter 5

Two types of signal conduction
within a single neuron
1. Passive (graded) electrotonic
conduction: depend on the
movement of ions along the two
faces of the plasma membrane;
decays with distance.
2. Active (regenerative) conduction
(AP): depend on the presence and
activity of biological molecules
such as voltage-gated ion channels;
transmit without loss of signal
strength.
Passive electrotonic
conduction decays with
distance
1. Cytoplasm resistance
2. Plasma membrane
resistance
3. Charges leaks out
Length constant () is
defined as the distance
over which a steadystate potential shows a
63% drop in
amplitude.
Propagation of a nerve
impulse (AP) along the
axon depends on
1. The passive cable properties
of an axon.
2. The electrical excitability of
Na+ channels in the axon
membranes.
Increasing conduction
velocity of AP
1. Increase axonal
diameter
2. Myelination
Conduction in Myelinated Axon
• Myelin prevents
movement of Na+
and K+ through the
membrane.
• Nodes of Ranvier
contain VG Na+ and
K+ channels.
• Saltatory
conduction (leaps).
• Fast rate of
conduction.
Nodes of Ranvier
One of the regularly spaced interruptions of
myelin sheath along an axon.
Saltatory conduction
Discontinuous conduction of action potentials that takes
place at the nodes of Ranvier in myelinated axons.
Synapse
• Functional connection between a
neuron and another cell.
• Different types of synapses involve:
– Axodendritic (b):
• Axon of one neuron and dendrite of
another neuron.
– Axosomatic (a):
• Axon of one neuron and cell body of
another neuron.
– Axoaxonic (c):
• Axon of 1 neuron and axon of another
neuron.
• Transmission in one direction only.
Two types of synapses for transmit information between
neurons
1. Electrical synapse
2. Chemical synapse
Electrical synapses
At electrical synapses, the presynaptic cell and
postsynaptic cell are connected by protein complexes
called gap junctions, which are made of of subunits called
connexins.
Electrical synapses provide rapid and faithful signal
transmission between cells, but a less flexible response
than chemical synapses.
Electrical Synapse
• Impulses can be
regenerated without
interruption in adjacent
cells.
• Gap junctions:
– Adjacent cells
electrically coupled
through a channel.
• Examples:
– Smooth and cardiac
muscle.
– CNS, retina
Chemical Synapse
• Presynaptic terminal (bouton) releases
a chemical (neurotransmitter).
• Synaptic transmission is through a
chemical gated channel.
Chemical Synapse
• Terminal bouton is
separated from
postsynaptic cell by
synaptic cleft.
• Neurotransmitters (NT) are
released from synaptic
vesicles.
• Amount of
neurotransmitter released
depends upon frequency of
AP.
Synaptic Transmission
• AP travels down axon to bouton.
• VG Ca++ channels open.
• Ca++ enters bouton down concentration
gradient.
• Ca++ activates calmodulin, which activates
protein kinase.
Synaptic Transmission
• NT is released and diffuses across synaptic
cleft.
• Neurotransmitter (ligand) binds to receptor
in postsynaptic cell.
• Chemical gated ion channel opens.
• EPSP: depolarization.
• IPSP: hyperpolarization.
• Neurotransmitter inactivated.
Chemical synapses
Signals are carried across the synaptic cleft between the
presynaptic and postsynaptic cells by the diffusion of
neurotransmitter molecules.
Fast direct chemical synapses: the transmitter receptor
proteins include the both the binding site for the
transmitter and an ion channel. Neurotransmitters are
synthesized in the axon terminals and stored in small
vesicles. These transmitters are typically small organic
molecules.
Slow indirect chemical synapses: the transmitter
receptor proteins act through intracellular messenger
systems to affect the conductance through ion channels.
The transmitters are typically large molecules
containing a single amino acid (biogenic amines) or
several amino acid residues (neuropeptide). They are
usually synthesized in the soma, packaged into large
vesicles, and transported to the axon terminal.
The onset of response is slower, but last longer (seconds
to hours)
Excitatory postsynaptic potential (epsp)
A change in the membrane potential of a postsynaptic cell that
increases the probability of an action potential in that cell.
Inhibitory postsynaptic potential (ipsp)
A change in the transmembrane potential of a postsynaptic cell
that reduces the probability of an action potential in that cell.
Excitatory postsynaptic potential (epsp)
The current are typically carried through Na+ or Ca2+.
Inhibitory postsynaptic potential (ipsp)
The current are typically carried through channels that are
permeable either to K+ or to Cl-.
Synaptic Integration
• EPSPS can summate,
producing AP.
– Spatial summation:
• Numerous boutons
converge on a single
postsynaptic neuron
(distance).
– Temporal summation:
• Successive waves of
neurotransmitter release
(time).
EPSP
• No threshold.
• Decrease resting
membrane potential.
– Closer to threshold.
• Graded in magnitude.
• Have no refractory
period.
• Can summate.
IPSP
• No threshold.
• Hyperpolarize postsynaptic
membrane.
• Increase membrane
potential:
– Further away from
threshold.
• Can summate.
• No refractory period.
Excitation and inhibition depend critically on the
nature of the local ionic gradients (properties of the
channel & identities of the ions that flow) and not on
the identity of the signaling molecule.
Presynaptic inhibition: Neuronal inhibition resulting from action
of an inhibitory terminal that synapses on the presynaptic
terminal of an excitatory synapse, which reduces the amount
of transmitter released.
1. Increasing gk and gCl in the presynaptic terminals
2. Reducing Ca2+ entry in the presynaptic terminals
Neurotransmitter releasing depends on
•
Depolarization of presynaptic membrane
•
More depolarization caused more transmitter to be released
•
Extracellular Ca2+ concentrations
Transmitter release steps
1. Mature vesicles move up to active
zones with assistance of cytoskeletal
protein actin and myosin.
2. Vesicle attached to membrane by the
sec6/8 and rab proteins (reversible)
3. Attached irreversibly by forming
SNARE complex
4. Synaptotagmin interacts with the
SNARE complex to produce rapid
fusion.
Classification of neurotransmitters
• Acetylcholine (ACh)
• Biogenic amines (norepinephrine,
dopamine, serotonin, histamine)
• Amino acids (r-aminobutyric acid,
glutamate, glycine)
• polypeptides (somatostatin, substance P,
LHRH)
• Novel messengers (ATP, NO, CO)
Acetylcholine (ACh) as
Neurotransmitter
• ACh is both an excitatory and
inhibitory NT.
• Causes the opening/closing of
chemical gated ion channels.
Ligand-Operated ACh
Channels
• Most direct
mechanism.
• Ion channel runs
through receptor.
• Receptor has 5
polypeptide subunits
that enclose ion
channel.
• 2 subunits contain
ACh binding sites.
• Permits diffusion of
Na+.
G Protein-Operated ACh
Channel
• Only 1 subunit.
• Ion channels are
separate proteins
located away from the
receptors.
• Binding of ACh
activates alpha G
protein subunit.
• Alpha subunit or the
beta-gamma complex
diffuses through
membrane until it binds
to ion channel, opening
it.
General events at G-protein coupled receptor
1. Neurotransmitter binds to the receptor protein
2. GDP is released from Ga subunit
3. GTP binds to the a protein cause dissociation of G-protein
from the receptor and bg from a subunits
4. Activated a subunit, or the beta-gama complex binds to the
effector molecules (signal transduction)
5. GTP was hydrolyzed to GDP by GTPase (termination of
signal)
6. Bound to GDP again, the a and bg form complex and bind to
the receptor.
At least three separate proteins contribute to slow, indirect
chemical synaptic transmission
1. Neurotransmitter receptor protein (seven transmembrane
domains)
2. Activated G proteins including a subunits or bg comlex,
3. Effector proteins (ion channels, enzyme for 2nd messenger)
G-proteins can function only if GTP is available
Nonhyrolyzable analog of GTP, GTPgS induce stable activation of
the Ga protein.
Acetylcholinesterase
• AChE:
• Enzyme that
inactivates ACh.
• Prevents
continued
stimulation.
Monoamines as NT
• Monoamine NTs:
–
–
–
–
Epinephrine
Norepinephrine
Serotonin
Dopamine
• Released by exocytosis from presynaptic
vesicles.
• Diffuse across the synaptic cleft.
• Interact with specific receptors in
postsynaptic membrane.
Mechanism of Action
•
•
•
•
•
Monoamine NT do not
directly open ion channels.
Act through second
messenger, cAMP.
Binding of norepinephrine
stimulates dissociation of
G protein alpha subunit.
Alpha subunit binds to
adenylate cyclase,
converting ATP to cAMP.
cAMP activates protein
kinase, phosphorylating
other proteins.
• Reuptake of monoamines
into presynaptic
membrane.
• Enzymatic degradation in
presynaptic membrane by
MAO.
• Enzymatic degradation in
postsynaptic membrane by
COMT.