Download BIO3420.2010.4NERVOUS SYSTEM Part2_3

NERVOUS SYSTEM, Parts 2 and 3
Neuron structure and function;
Electrical and chemical synapses;
Transmission of signals;
Neurotransmitters;
Integration at synapses.
Chapter 4; 29.09. - 01.10.2010
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Voltage-Gated Channels and the AP
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Figure 4.12
Fig. 4.11 Model for the action of voltage-gated Na+ channels
Na+ Channels Have Two Gates
 Activation gate
 Voltage dependent
 Opens when membrane reaches threshold
 Inactivation gate
 Time-dependent
 Closes after brief time
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Characterization of Na+ channels
•use of neurotoxins
block Na+ channels with tetrodotoxin (TTX)
(neurotoxic paralytic poison found in pufferfish,
blue-ringed octopus)
with TTX in ECF-only inward current affected
no effect if TTX in ICF
1 molecule of TTX blocks 1 Na+ channel
can estimate # of Na+ channels from [TTX]
CELL MEMBRANE HAS PROPERTIES OF
CAPACITANCE & CONDUCTANCE
CAPACITANCE (C)
capacity to store electrical charge by electrostatic means
ion-impermeant lipid bilayer separates charge
high electrical resistance
thin membrane
CONDUCTANCE
(g)
reciprocal of resistance
measure of permeability to ions
membrane conductance for ion species x = gx
gx = Ix
Ix is current caried by ion x
emfx
emfx is electromotive force acting on ion x
Action Potentials Travel Long Distances
Elecrotonic
current
spread
and
Regenerating
action
potentials
Diversity of
channels in
neurons and
animal species
e.g. Na+ channels
K+ channels
Ca++ channels
etc.
Fig.4.13
PROPAGATION OF AP ALONG AN AXON
AP travels unidirectionally
AP travels along axon without decrement
Propagation depends on electrotonic conduction.
Comparison of properties of Na+ and K+ voltage-activated channels with Na+ / K+ pump
Sodium and potassium
Sodium pump
channels
___________________________________________________________________________
Direction of ion
Down the electrochemical
Against the
movements
gradient
electrochemical
gradient
Source of energy
Pre-existing concentration
ATP
gradient
Voltage dependence
Regenerative link between
Independent of
+
potential and Na conductance
potential
Selectivity
Tetrodotoxin blocks Na+
channels
Ouabain has no effect
Li+ is not distinguished from Na+
Density of distribution
in the membrane
Squid axon
290 TTX binding sites per m2
Max rate of Na+ movement
100 000 pmol/cm2 s during rising
phase of AP
Metabolic inhibitors
No effect
Blocking agents
Tetrodotoxin has no
effect
Oubain blocks
Li+ is pumped more
slowly than Na+
Squid axon
4000 ouabainbinding sites per m2
60 pmol/cm2 s at room
temperature
Cyanide blocks as soon
as ATP is exhausted
Cable Properties of Axons
Similar physical principals govern current flow
through axons and undersea telephone cables
Current (I)
 Amount of charge moving past a point at a given
time
 A function of the voltage (V) drop across circuit
and the resistance (R) of circuit
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Cable Properties of Axons
Voltage (V)
 Difference in electrical potential
Resistance (R)
 Force opposing flow of electrical current
Ohm’s law: V = I  R
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Cable Properties of Axons
An axon behaves like an electrical circuit
 Ions moving through voltage-gated channels cause
current across membrane
 Current spreads electrotonically along axon
 Some current leaks out of axon and flows
backwards along outside of axon, completing
circuit
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Cable Properties of Axons
Each area of axon consists of an electrical circuit
 Three resistors:
 Extracellular fluid (Re)
 Membrane (Rm)
 Intracellular fluid (Ri)
 A capacitor (Cm)
 Stores electrical charge;
 Two conducting materials (ICF and ECF)
 Insulating layer (phospholipids)
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Cable properties of the axon
LOCAL CIRCUIT CURRENTS
Current can take TWO paths:
• flow out across membrane
• flow along axoplasm
creates local circuit currents
as the result of
passive electrotonic
transmission
Fig. 4.20
Ohm’s law
V = IR
I = V/R
Voltage Decreases with Distance
Change in membrane potential (voltage) during AP
decreases over distance due to resistance
 Conduction with decrement
 Higher resistance of intracellular and extracellular
fluids causes greater decrease in voltage along axon
 Lower resistance of membrane causes greater
decrease in voltage along axon
 K+ leak channels (always open)
 Some + charge leaks out
 Number of K+ leak channels will affect current loss and
voltage decrease along axon
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l and the Speed of Conduction
Axonal conduction is a combination of electrotonic
current flow and ions flowing through voltage-gated
channels during AP
 Electrotonic current flow much faster than opening
of voltage-gated channels
 Electronic current flow decreases over distance
Higher l allows more electrotonic current flow and
faster speed of conduction
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Axon Membrane Capacitance
Capacitance
 Quantity of charge needed to create a potential
difference between two surfaces of a capacitor
Depends on three features of the capacitor:
 Material properties
 Generally the same in cells (lipid bilayer)
 Area of two conducting surfaces
 Larger area increases capacitance
 Thickness of insulating layer
 Greater thickness decreases capacitance
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Length Constant (l) of Axons
Distance over which membrane potential will
decrease to 37% (1/e) of its original value
Variables affecting length constant:
 Resistance of cell membrane (rm)
 Resistance of intracellular fluid (ri)
 Resistance of extracellular fluid (ro)
 ro is usually low and constant; and is often ignored
 l is largest when rm is high and ri is low
l  rm /( ri  r )
o
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l  rm / ri
Time Constant (t)
Time over which membrane potential will decay to
37% of its maximal value
 How well does the membrane “hold” its charge?
Variables affecting time constant:
 Resistance of cell membrane (rm)
 Capacitance of the cell membrane (cm)
 t = rmcm
 Low rm or cm result in low t
 Capacitor becomes full faster
 Faster depolarization
 Faster conduction
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Myelination
 Vertebrate neurons are myelinated
 Myelin
 Insulating layer of lipid-rich Schwann cells wrapped
around axon
 Reduce “leakage” of charge across membrane
 Schwaan cells are a type of Glial cell
 Cells other than neurons that support neuron function
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Myelination
 Nodes of Ranvier
 Areas of exposed axonal membrane between Schwann
cells
 Internodes
 The myelinated region
 Saltatory conduction
 APs “leap” from node to node
 APs occur at nodes of Ranvier, and electrotonic
current spread through internodes
 This type of conduction is very rapid
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Myelinated Neurons in Vertebrates
Disadvantage of large axons
 Take up a lot of space which
 Limits number of neurons that can be packed into
nervous system
 Large volume of cytoplasm makes them expensive
to produce and maintain
Myelin enables rapid signal conduction in compact
space
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Myelin Increases Conduction Speed
Increased membrane resistance
 Insulators decrease current loss through leak
channels, increasing the length constant
Decreased membrane capacitance
 Increased thickness of insulating layer reduces
capacitance, decreasing the time constant
High length constant and low time constant increase
conduction speed
Nodes of Ranvier are needed to boost depolarization
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•Differences in conduction speed among axons
Speed of conduction increases with
•myelination
SALTATORY CONDUCTION
•axon diameter
segmental insulation
internodal distances 0.2 – 2 mm
no Na+ channels under myelin sheath
no contact with ECF except at nodes
MYELIN SHEATH causes
•increase in membrane Resistance
•decrease in membrane Capacitance
•depolarization spreads farther and faster
Fig. 4.14
N.B. multiple sclerosis
Unidirectional Signals
 Action potentials start at the axon hillock and travel
towards the axon terminal
 “Up-stream” Na+ channels (just behind the region
of depolarization) are in the absolute refractory
period
 The absolute refractory period prevents backward
(retrograde) transmission and summation of APs
 Relatively refractory period also contributes by
requiring a very strong stimulus to cause another AP
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Information Transfer by AP
 AP frequency carries information
 AP frequency increases with stronger stimuli
 Magnitude of each AP does not change
 Maximum frequency is limited by the absolute
refractory period
 Mammalian nerves can conduct 500–1000 action
potentials per second
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Fig. 7.3
Fig. 7.5 Structure of the vertebrate
central nervous system
SIGNAL TRANSMISSION
The Synapse
 Signal transmission from neuron to another cell
 Synapse
 Presynaptic cell, synaptic cleft, and postsynaptic cell
 Synaptic cleft
 Space between the presynaptic and postsynaptic cell
 Postsynaptic cell
 May be a neuron, muscle cell, or endocrine cell
 Neuromuscular junction
 Synapse between a motor neuron and a skeletal
muscle cell
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SYNAPTIC TRANSMISSION
SYNAPSE : Junction between excitable cells, enables cell-to-cell communication
1) ELECTRICAL (uncommon)
e.g. fish escape response neuron
vertebrate heart
direct spread of electrical signal (AP) via GAP JUNCTIONS
e.g. motor neuron  muscle
sensory neuron  interneuron
signal carried across synaptic cleft by neurotransmitter chemical
2) CHEMICAL (common)
Fig. 4.26
Electrical and Chemical Synapses
Electrical synapse
Chemical synapse
Rare in complex animals
Common in complex animals
Common in simple animals
Rare in simple animals
Fast
Slow
Bi-directional
Unidirectional
Postsynaptic signal is similar to
presynaptic
Postsynaptic signal can be different
Excitatory
Excitatory or inhibitory
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Structural Diversity of Chemical Synapses
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Figure 4.27
Events of signal transmission at a chemical synapse
Fig. 4.16
1. Electrical signal in presynaptic cell
2. Chemical signal in synaptic clef
3. Electrical signal in postsynaptic cell
CHEMICAL SYNAPSES and NEUROMUSCULAR JUNCTIONS
Amount of Neurotransmitter Released
 [Ca2+]i is affected by AP frequency
 More open voltage-gated Ca2+ channels  [Ca2+]i
 Factors that lower intracellular [Ca2+]i
 Binding with intracellular buffers  [Ca2+]i
 Ca2+ ATPases  [Ca2+]i
 High AP frequency  Ca2+ influx is greater than
removal   [Ca2+]i  many synaptic vesicles
release their contents  high [neurotransmitter] in
synapse
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Synthesis and recycling of acetylcholine (Ach) at the synapse
Fig.4.17
Neurotransmitters
Characteristics of neurotransmitters
 Synthesized in neurons
 Released at presynaptic cell following
depolarization
 Bind to a postsynaptic receptor and cause an effect
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Neurotransmitters
More than 50 known substances
Categories





Amino acids
Neuropeptides
Biogenic amines
Acetylcholine
Miscellaneous (gases, purines, etc.)
A single neuron can produce and release more than
one neurotransmitter
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Neurotransmitters
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Table 4.4
Neurotransmitter Action
Inhibitory neurotransmitters
 Cause hyperpolarization of membrane
 Inhibitory postsynaptic potential (IPSP)
 Make postsynaptic cell less likely to generate
an AP
Excitatory neurotransmitters
 Cause depolarization of membrane
 Excitatory postsynaptic potential (EPSP)
 Make postsynaptic cell more likely to generate
an AP
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Postsynaptic Cells
 Postsynaptic cells have specific receptors for
neurotransmitters
 Example: nicotinic ACh receptors
 Similar to specific hormone receptors on target cells
 Binding of neurotransmitter to receptor alters ion
permeability of postsynaptic cell
 Change in membrane potential of postsynaptic cell
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Transmission of Signal Strength at Synapse
 Response of postsynaptic cell influenced by
amount of neurotransmitter in synapse and number
of receptors
 Amount of neurotransmitter
 Rate of release – rate of removal
 Release determined by frequency of APs
 Removal determined by
 Passive diffusion out of synapse
 Degradation by synaptic enzymes
 Uptake by surrounding cells
 Number of receptors
 Density of receptors on postsynaptic cell
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Neurotransmitter Receptor Function
 Ionotropic receptors
 Ligand-gated ion
channels
 Fast
 Example: nicotinic
Ach receptor
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Figure 4.28a
Neurotransmitter Receptor Function
 Metabotropic receptors
 Receptor changes shape
 Formation of second
messenger
 Alters opening of ion
channel
 Slow
 May lead to long-term
changes via other cellular
functions
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Figure 4.28b
Receptors for Acetylcholine
Cholinergic receptors
 Nicotinic receptor
 Ionotropic
 Muscarinic receptor
 Metabotropic
 Linked to ion channel function via G-protein
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Receptors for Acetylcholine
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Figure 4.29
Receptors for Acetylcholine
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Table 4.5
Receptors for Norepinephrine
 Adrenergic receptors
 Alpha ()
 Several isoforms
 Metabotropic
 Linked to ion channel function via G-protein
 Beta ()
 Several isoforms
 Metabotropic
 Linked to ion channel function via G-protein
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Adrenergic Receptors
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Table 4.6
Synaptic Plasticity
 Change in synaptic function in response to patterns
of use
 Synaptic facilitation
 Repeated APs result in increased Ca2+ in terminal
 Increased neurotransmitter release
 Synaptic depression
 Repeated APs deplete neurotransmitter in terminal
 Decreased neurotransmitter release
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Synaptic Plasticity
 Post-tetanic potentiation (PTP)
 After train of high frequency APs there is increased
neurotransmitter release
 Exact mechanism unknown, but believed to involve
changes in Ca2+ in terminal
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Post-tetanic Potentiation (PTP)
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Figure 4.32
Evolution of Neurons
 Only metazoans have neurons
 Other organisms have electrical signaling
 Algae have giant cells that can generate APs using
Ca2+ activated Cl– channels
 Plants have APs involving Ca2+ that travel through the
xylem and phloem
 Paramecium can change direction as a result of APs
produced by Ca2+ channels
 Only metazoans have voltage-gated Na+ channels
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