Ch 8: Neurons: Cellular and Network Properties

1
Ch 8 Neurons Cellular and Network Properties
Objectives

• Describe the Cells of the NS
• Explain the creation and propagation of an
  electrical signal in a nerve cell
• Outline the chemical communication and signal
  transduction at the synapse

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The afferent and efferent axons together form the

• Central nervous system
• Autonomic division of the nervous system
• Somatic motor division of the nervous system
• Peripheral nervous system
• Visceral nervous system

3
Autonomic neurons are further subdivided into the

• Visceral and somatic divisions
• Sympathetic and parasympathetic divisions
• Central and peripheral divisions
• Visceral and enteric divisions
• Somatic and enteric divisions

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Organization of NS
Compare to fig 8-1
Afferent division
Efferent division
New 3rd division Enteric NS
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Processes or appendages that are part of neurons
include

• Axons
• Dendrites
• Neuroglia
• A and B
• A, B and C

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Cells of NS
Fig 8-2

• Nerve cell Neuron
• Support cells Neuroglia
• Neuron functional unit of nervous system
• excitable
• can generate carry electrical signals
• Neuron classification either
  structural or functional (?)

Figs 8-3
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Functional categories of neurons include

• Afferent neurons
• Sensory neurons
• Interneurons
• Efferent neurons
• All of these are included as functional
  categories of neurons

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Axonal Transport

• What is it? Why is it necessary?
• Slow axonal transport (.2 - 2.5 mm/day)
• Carries enzymes etc. that are not quickly
  consumed Utilizes axoplasmic flow
• Fast axonal transport (up to 400 mm/day)
• Utilizes kinesins, dyneins and microtubules
• Actively walks vesicles up or down axon

Fig 8-4
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Axonal Transport of Membranous Organelles
retrograde
anterograde
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Which of the following is the main glial cell of
the PNS?

• Microglia cell
• Astrocyte
• Schwann cell
• Oligodendrocyte
• All of these are found in the PNS

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Neuroglia cells
In CNS

• Oligodendrocytes (formation of myelin)
• Astrocytes (BBB, K uptake)
• Microglia (modified M?)
• (Ependymal cells)
• Schwann cells (formation of myelin)
• Satellite cells

In PNS
See Fig 5-8
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Electrical Disequilibrium (Resting Membrane
Potential)
Ch 5, p156 on

• Membrane potential unequal distribution of
  charges (ions) across cell membrane
• K is major intracellular cation
• Na is major extracellular cation
• Water conductor / cell membrane

15
Review of Solute Distribution in Body Fluids
Na high
ECF
ICF
K high
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Electro-Chemical Gradients

• Allowed for by cell membrane
• Created via
• Active transport
• Selective membrane permeability to certain ions
  and molecule

Fig 5-36
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Separation of Electrical Charges
Physiol. Measurements are always on relative
scale !
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Resting Membrane Potential Difference

• All cells have it
• Resting ? cell at rest
• Membrane Potential ? separation of charges
  creates potential energy
• Difference ? difference between electrical
  charge inside and outside of cell (ECF by
  convention 0 mV)
• Measuring membrane potential differences

Fig 5-37
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Measuring Membrane Potential Differences
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Ions Responsible for Membrane Potential

• Cell membrane
• impermeable to Na, Cl - Pr
• permeable to K
• ? K moves down concentration gradient (from
  inside to outside of cell)
• ? Excess of neg. charges inside cell
• ? Electrical gradient created
• Neg. charges inside cell attract K back into
  cell

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Equilibrium Potential for K

• Membrane potential difference at which movement
  down concentration gradient equals movement down
  electrical gradient
• Definition electrical gradient equal to and
  opposite concentration gradient
• Equilibrium potential for K -90 mV

Fig 5-38
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Potassium Equilibrium Potential
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Equilibrium Potential for Na

• Assume artificial cell with membrane permeable to
  Na but to nothing else
• Redistribution of Na until movement down
  concentration gradient is exactly opposed by
  movement down electrical gradient
• Equilibrium potential for Na 60 mV

Fig 5-39
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Na Equilibrium Potential
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On the planet Endor (where all known physical
laws are obeyed), animals have evolved a unique
nervous system. Neurons in these animals are
exclusively permeable to Ca2 at their normal
resting membrane potential. In these animals,
there is a 10-fold higher Ca2 concentration
outside the cell than there is inside. The
resting membrane potential of these cells could
be approximately

• 58 mV
• 29 mV
• 0 mV
• 29 mV.
• Either A or B is possible

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Resting Membrane Potential
of most cells is between -50 and -90 mV (average
-70 mV)

• Reasons
• Membrane permeability K gt Na at rest
• Small amount of Na leaks into cell
• Na/K-ATPase pumps out 3 Na for 2 K pumped
  into cell

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Change in Ion Permeability

• leads to change in membrane potential
• Terminology

Stimulus Depolarization Repolarization Hyperpolari
zation
Fig 5-41
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Explain

• Increase in membrane potential
• Decrease in membrane potential
• What happens if cell becomes more permeable to
  potassium
• Maximum resting membrane potential a cell can
  have

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Insulin Secretion

• Membrane potential changes play important role
  also in non-excitable tissues!
• ?-cells in pancreas have two special channels
• Voltage-gated Ca2 channel
• ATP-gated K channel

Fig 5-42
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Resting membrane potential changes are important
in

• Neurons.
• muscle cells.
• In all kinds of different types of cells.
• Both A and B are correct.
• A, B and C are correct.

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What is the direction of the driving force(s) for
the movement of sodium ions when a nerve cell is
at rest?

• Inward chemical gradient
• Outward electrical gradient
• Outward chemical gradient
• Both A and B
• Both B and C

34
If the membrane potential is equal to chlorides
equilibrium potential, in which direction will
Cl- ions move if a chloride channel opens while
the cell remains at resting membrane potential

• Inward
• Outward
• Ions move equally in both directions
• No ions will move through the channel
• Three chloride ions will move out for every two
  chloride ions that move in.

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Electrical Signals in Neurons
Ch 8 p. 246

• Changes in membrane potential are the basis for
  electrical signaling
• Only nerve and muscle cells are excitable (
  able to propagate electrical signals)
• GHK EquationResting membrane potential
  combined contributions of the conc. gradients and
  membrane permeability for Na, K (and Cl-)

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Control of Ion Permeability

• Gated ion channels alternate between open and
  closed state
• Mechanically gated channels
• Chemically gated channels
• Voltage-gated channels
• Net movement of ions de- or hyperpolarizes cell
• 2 types of electrical signals
• Graded potentials, travel over short distances
• Action potentials, travel very rapidly over
  longer distances

7 system CD-ROM
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Four Basic Components of Signal Movement Through
Neuron

• Input signal (graded potential)
• Integration of input signal at trigger zone
• Conduction signal to distal part of neuron (
  Action Potential)
• Output signal (usually neurotransmitter)

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Input Signal Graded Potentials

• Location ?
• Strength ( amplitude) strength of
  triggering event
• Travel over short distances to trigger zone
• Diminish in strength as they travel
• May be depolarizing (EPSP) or hyperpolarizing
  (IPSP)

Fig 8-7
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Graded Potentials
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Subthreshold potential vs. Suprathreshold
potential
Fig 8-8
Graded potential starts here
Trigger zone
AP
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Conduction Signals Action Potentials (AP)

• Location ?
• Travel over long distances
• Do not loose strength as they travel
• Are all identical (all-or-none principle) 100mV
  amplitude
• Represent movement of Na and K across membrane

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Ion Movement across Cell Membrane During AP

• Sudden increase in Na permeability
• Na enters cell down electrochemical gradient (
  feedback loop for .5 msec)
• Influx causes depolarization of membrane
  potential electrical signal
• What stops feedback loop?

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Na Channels in Axon Have 2 Gates

• Activation gate and Inactivation gate
• Na entry based on pos. feedback loop ? needs
  intervention to stop
• Inactivation gates close in delayed response to
  depolarization
• ? stops escalating pos. feedback loop

Fig 8-10
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Model of Activation and Inactivation Gates
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AP-Graph

• has 3 phases
• Rising (Na permeability ?)
• Falling (K permeability ?)
• Undershoot or Hyperpolarization

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Graded potentials

• Produce an effect that increases with distance
  from the point of stimulation
• Produce an effect that spreads actively across
  the entire membrane surface
• May involve either depolarization or
  hyperpolarization
• Are all-or-none
• All of the above

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The principal cause of early repolarization of a
nerve fiber after an adequate stimulus has been
applied is

• An increase in the diffusion of K into the
  neuron
• An increase in the diffusion of Na out of the
  neuron
• And increase in the diffusion of Na into the
  neuron
• And increase in the diffusion of K out of the
  neuron
• A decrease in the diffusion of Na into the neuron

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Absolute Relative Refractory Periods
No movement of Na possible

• Na channels
• reset to resting
• state, K channels
• still open higher
• than normal
• Stimulus
• necessary

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Refractory Periods

• Limit signal transmission rate (no summation!)
• Assure one way transmission!

Forward current excites, backward current does
NOT re-excite !
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Conduction speed depends on . . . .

• Axon diameter
• Size constraints on axons become problem with
  increasing organismal complexity
• Membrane resistance
• High resistance of myelin prevents current flow
  between axon and ECF ? saltatory conduction from
  node to node

Fig 8-16
Fig 8-22
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Axon Diameter
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Signal Transduction in Myelinated Axon
Fig. 8-1
Demyelination diseases (E.g. ?)
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Output Signal Communication at Synapses

• Synapse point where neuron meets target cell
  (e.g. ?)
• 2 types
• chemical
• electrical
• 3 components of chemical synapse
• presynaptic cell
• synaptic cleft
• postsynaptic cell

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Chemical Synapses

• Majority of synapses
• Use neurotransmitters to carry info from cell to
  cell
• Axon terminals have mitochondria synaptic
  vesicles containing neurotransmitter

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Events at the Synapse

• AP reaches axon terminal
• Voltage-gated Ca2 channels open
• Ca2 entry
• Exocytosis of neurotransmitter containing vesicles

Ca2 Signal for Neurotransmitter Release
Fig 8-20
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3 Classes of Neurotransmitters (of 7)

• Acetyl Choline
• Made from Acetyl CoA and choline
• Synthesized in axon terminal
• Quickly degraded by ACh-esterase
• Cholinergic neurons and receptors Nicotinic and
  muscarinic
• Amines
• Serotonin (tryptophane) and Histamine (histidine)
• Dopamine and Norepinephrine (tyrosine)
• Widely used in brain, role in emotional behavior
  (NE used in ANS)
• Adrenergic neurons and receptors - ? and ?
• Gases
• NO (nitric oxide) and CO

Fig 8-21
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Synthesis and Recycling of ACh at Synapse
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Postsynaptic Responses

• Can lead to either EPSP or IPSP (p.252)
• Any one synapse can only be either excitatory or
  inhibitory
• Fast synaptic potentials
• Opening of chemically gated ion channel
• Rapid of short duration
• Slow synaptic potentials
• Involve G-proteins and 2nd messengers
• Can open or close channels or change protein
  composition of neuron

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Integration of Neural Information Transfer
Fig 8-25

• Multiple graded potentials are integrated at axon
  hillock to evaluate necessity of AP
• Spatial Summation stimuli from different
  locations are added up
• Temporal Summation sequential stimuli added up

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Spatial Summation
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Temporal Summation
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Synapse most vulnerable step in signal
propagation

• Many disorders of synaptic transmission, e.g.
• Myasthenia gravis (PNS)
• Parkinsons (CNS)
• Schizophrenia (CNS)
• Depression (CNS)

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The End
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A(n) ________ functions to passively move ions
across a membrane against the direction of their
active transport.

• pump
• channel
• symporter
• antiporter
• exchanger

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When it becomes harder for the neuron to fire, is
has become

• refracted
• polarized
• hyperpolarized
• depolarized
• repolarized

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Starting with the arrival of the AP at the
terminal of a motor neuron and ending with the
beginning of an EPSP which of the following is a
correct temporal sequence?

• vesicle fusion ? inward Ca2 current ?
  transmitter exocytosis ? synaptic delay ?
  postsynaptic channel opens ? transmitter binds to
  postsynaptic receptor
• Inward Ca2 current ? vesicle fusion ?
  postsynaptic channels open ? transmitter
  exocytosis ? synaptic delay ? NT binds to
  postsynaptic receptor
• Inward Ca2 current ? vesicle fusion ?
  transmitter exocytosis ? transmitter binds to
  postsynaptic receptor ? postsynaptic channel
  opens
• transmitter binds to postsynaptic receptor ?
  postsynaptic channel opens ? hydrolysis of
  transmitter ? postsynaptic channel closes

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When an adequate stimulus is applied to an axon

• The amplitude of the AP is directly proportional
  to the strength of the applied stimulus
• The amplitude of the AP is inversely proportional
  to the strength of the applied stimulus
• The speed of the nerve impulse conduction is
  inversely proportional to the diameter of the
  nerve fiber
• The amplitude of the AP does not vary with the
  strength of the stimulus
• The first gate to open is the Na inactivation
  gate

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Toms father suffers a stroke that leaves him
partially paralyzed on his right side. What type
of glial cell would you expect to find in
increased numbers in the damaged area of the
brain that is affected by the stroke?

• Astrocytes
• Oligodendrocytes
• Schwann cells
• Ependymal cells
• Microglia

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The primary problem in hypokalemia is that

• Neurons are harder to excite because their
  resting potential is hyperpolarized
• Neurons are hyper-excitable because their resting
  potential is closer to threshold
• Neurons respond too quickly to smaller graded
  potentials
• A and C
• B and C

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The basis of neural integration is

• Addition of postsynaptic potentials overlapping
  in time and space
• Command signals from central pattern generators
• Spontaneous activity in pacemaker neurons
• The area under the curve of postsynaptic
  potentials overlapping in time and space
• All of the above

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How would blocking the ability for retrograde
transport in an axon affect the activity of a
neuron?

• The neuron would not be able to produce NT
• The neuron would not be able to have APs
• The cell body would not be able to export
  products to the axon terminal
• The cell body would not be able to respond to
  changes in the distal end of the axon
• The neuron would be unable to depolarize when
  stimulated.