Chapter 4
Principles of Neural and
Hormonal Communication
• Write and answer detailed questions about how
membrane potentials are propagated, converted to
chemical signals (neurotransmitters) at synapses,
and create postsynaptic potentials. This will be
measured by exams, quizzes and student
generated questions in class discussions.
Outline
•
•
•
•
•
•
•
Graded Potentials
Action Potentials
Synapses and integration
Intracellular communication
Signal Transduction
Hormonal Communication
Nervous vs. Endocrine System
Communication is critical for the survival of the
cells that compose the body.
Two major regulatory systems of the body –
nervous and endocrine - communicate with the
cells/tissues/organs/systems they control.
Neural communication
Hormonal communication
Neural Communication
• Nerve and muscle cells are excitable tissues.
• Can alter their membrane permeabilities.
• Permeability changes lead to membrane
potential changes.
• Potential changes act as electrical signals.
• Electrical signals are necessary for normal nerve
and muscle function.
Membrane potential (mV)
Neural Communication
+20
+10
0
–10
–20
–30
–40
–50
–60
–70
–80
–90
•
Depolarization (decrease in potential;
membrane less negative)
Repolarization (return to resting potential
after depolarization)
Hyperpolarization (increase in
potential; membrane more negative)
Resting potential
Membrane electrical states
– Polarization
• Any state when the membrane potential is other than 0mV
– Depolarization
• Membrane becomes less polarized than at resting potential
– Repolarization
• Membrane returns to resting potential after having been depolarized
– Hyperpolarization
• Membrane becomes more polarized than at resting potential
Time (msec)
Fig. 4-1, p. 90
Voltage clamp
•
•
•
The technique allows an experimenter to "clamp" the cell potential at a chosen value.
This makes it possible to measure how much ionic current crosses a cell's membrane at any given
voltage.
This is important because many of the ion channels in the membrane of a neuron are voltage
gated ion channels, which open only when the membrane voltage is within a certain range.
https://www.youtube.com/watch?v=Wd_gKJoo25Y
Kenneth Cole[2] and George Marmount
Patch clamp
•
•
•
•
•
A patch-clamp microelectrode is a micropipette with a relatively large tip diameter.
The microelectrode is placed next to a cell, and gentle suction is applied through the
microelectrode to draw a piece of the cell membrane (the 'patch') into the
microelectrode tip; the glass tip forms a high resistance 'seal' with the cell membrane.
This can be used for studying the activity of the ion channels that are present in the
patch of membrane.
If more suction is now applied, the small patch of membrane in the electrode tip can
be displaced, leaving the electrode sealed to the rest of the cell.
This "whole-cell" mode allows very stable intracellular recording.
https://www.youtube.com/watch?v=8
LDO0hWWc0Q
This technique was developed by Erwin Neher and Bert
Sakmann who received the Nobel Prize in 1991.
Channels
• Leak channels
– Unregulated passage of ions
• Gated channels
–
–
–
–
Voltage gated
Chemically gated
Mechanically gated
Thermally gated
• These channels create and alter membrane potentials
• Two kinds of potential change
– Graded potentials
• Serve as short-distance signals
– Action potentials
• Serve as long-distance signals
Graded Potential
• Occurs in small, specialized region of excitable cell
membranes
• Magnitude of graded potential varies directly with the
magnitude of the triggering event
• Die out over short distances
Fig. 4-2, p. 87
Current Flow During a Graded Potential
Graded Potentials
Examples of graded potentials:
•
•
•
•
•
Postsynaptic potentials
Receptor potentials
End-plate potentials
Pacemaker potentials
Slow-wave potentials
Action Potentials
• Brief, rapid, large (100mV) changes in
membrane potential during which potential
actually reverses
• Involves only a small portion of the total
excitable cell membrane
• Do not decrease in strength as they travel from
their site of initiation throughout remainder of cell
membrane
Membrane potential (mV)
+70
+60
+50
+40
+30
+20
+10
0
–10
20
–30
–40
–50
–60
–70
–80
–90
Action potential
Threshold potential
Resting potential
After hyperpolarization
Time (msec)
1 msec
Slow depolarization
to threshold
Fig. 4-4, p. 94
VOLTAGE-GATED SODIUM CHANNEL
VOLTAGE-GATED POTASSIUM CHANNEL
Activation
gate
ECF
Plasma
membrane
ICF
Activation gate
Inactivation gate
(a) Closed but
(b) Open
capable of opening (activated)
Rapid
opening
triggered
at threshold
Slow
closing
triggered
at threshold
(c) Closed and not
capable of opening
(inactivated)
(d) Closed
Delayed
opening
triggered
at threshold
(e) Open
Fig. 4-5, p. 95
ANIMATION: Action Potential
Action Potentials
• When membrane reaches threshold potential
– (-50 to-55mv)
– Voltage-gated channels in the membrane
undergo conformational changes
– Flow of sodium ions into the ICF reverses the
membrane potential from -70 mV to +30 mV
– Flow of potassium ions into the ECF restores the
membrane potential to the resting state
Action Potentials
• Additional characteristics
– Sodium channels open during depolarization by
positive feedback.
– When the sodium channels become inactive, the
channels for potassium open. This repolarizes
the membrane.
– As the action potential develops at one point in
the plasma membrane, it regenerates an identical
action potential at the next point in the
membrane.
– Therefore, it travels along the plasma membrane
undiminished.
4
Na+ channel closes and is inactivated
(activation gate still open; inactivation
gate closes)
K+ channel opens
(activation gate opens)
Na+ channel
reset to closed
but capable
of opening
(activation
gate closes;
inactivation
gate opens)
Membrane potential (mV)
Na+
channel
opens and
is activated
(activation
gate opens;
inactivation
gate already
open)
3
K+ voltage-gated channel closed
(activation gate closed)
5
2
ECF
Threshold potential
6
1
8
7
ICF
K+ channel
closes
(activation
gate closes)
Resting potential
Depolarizing
triggering event
Time (msec)
Na+ voltage-gated channel closed
(activation gate closed; inactivation gate open)
Fig. 4-7a, p. 96
Action Potentials
The Na+/K+ pump gradually restores the
concentration gradients disrupted by action
potentials.
• Sodium is pumped into the ECF
• Potassium is pumped into the ICF
• Refractory period keeps the action potential going in one
direction and limits the Ap frequency
• All or none
• Frequency and line coding
Table 4-1 p101
Action Potentials
• The Na+–K+ pump gradually restores the ions
that moved during the action potential.
• After an impulse has occurred in a patch of
membrane, the membrane enters its refractory
period.
• It is impossible to re-stimulate the patch of
membrane until it has recovered from its
refractory period.
Refractory Periods
• Absolute refractory period- period of time
when a patch of membrane cannot be restimulated no matter how strong the stimulus.
• Relative refractory period- period of time
during which a patch of membrane can only be
re-stimulated by a stronger than normal
stimulus.
• Refractory periods ensure the one-way
propagation of action potentials.
Previous active
area returned to
resting potential
New active area
at peak of action
potential
“Backward” current
flow does not reexcite
previously active area
because this area is
in its refractory period
New adjacent inactive area
into which depolarization
is spreading; will soon reach
threshold
“Forward” current flow excites
new inactive area
Direction of propagation
of action potential
Fig. 4-10, p. 101
Neuron
• Once initiated, action potentials are conducted
throughout a nerve fiber
• Action potentials are propagated from the axon
hillock to the axon terminals
• Basic parts of neuron (nerve cell)
– Cell body
– Dendrites
– Axon
Neuron
Neuron
• Cell body
– Houses the nucleus and organelles
• Dendrites
– Project from cell body and increase surface area
available for receiving signals from other nerve
cells
– Signal toward the cell body
Dendrite and cell body serve as the neurons input
zone.
Neuron
• Axon
– Nerve fiber
– Single, elongated tubular extension that conducts action
potentials away from the cell body
– Conducting zone of the neuron
– Collaterals
• Side branches of axon
– Axon hillock
• First portion of the axon plus the region of the cell body fro m
which the axon leaves
• Neuron’s trigger zone
– Axon terminals
• Release chemical messengers that simultaneously influence
other cells with which they come into close association
• Output zone of the neuron
Action Potentials
• Two types of propagation
– Contiguous conduction
• Conduction in unmyelinated fibers
• Action potential spreads along every portion of
the membrane
– Saltatory conduction
• Rapid conduction in myelinated fibers
• Impulse jumps over sections of the fiber
covered with insulating myelin
Contiguous Conduction
Adjacent area
that was
brought to
Previous active threshold by
area returned
local current
to resting
flow; now
potential; no
active at peak
longer active; in of action
refractory period potential
New adjacent
inactive area
into which
depolarization is
spreading; will
soon reach
threshold
Remainder of axon
still at resting potential
Fig. 4-9b, p. 100
Contiguous Conduction
Adjacent inactive area
Active area at into which depolarization
peak of action is spreading; will soon
Remainder of axon
potential
reach threshold
still at resting potential
Graded
potential
> threshold
Local current flow that depolarizes
adjacent inactive area from resting
potential to threshold potential
Direction of propagation of action potential
Fig. 4-9a, p. 100
Saltatory Conduction
Nodes of Ranvier
Myelin sheath
Myelin
sheath
Axon
Axon of neuron
Plasma
membrane
(a) Myelinated fiber
Fig. 4-12a, p. 103
Myelin
sheath
Voltage-gated
Na+ and K+
channels
Axon
Node of
Ranvier
Fig. 4-12d, p. 103
Saltatory Conduction
• Propagates action potential faster than
contiguous conduction because action potential
does not have to be regenerated at myelinated
section
• Myelinated fibers conduct impulses about 50
times faster than unmyelinated fibers of
comparable size
• Myelin
– Primarily composed of lipids
– Formed by oligodendrocytes in CNS
– Formed by Schwann cells in PNS
Active node at peak
of action potential
Adjacent inactive node
into which depolarization
is spreading; will soon
reach threshold
Remainder of nodes
still at resting potential
Local current flow that
depolarizes adjacent inactive
node from resting to threshold
Direction of propagation
of action potential
Fig. 4-13, p. 104
Regeneration of Nerve Fibers
• Regeneration of nerve fibers depends on its
location
• Schwann cells in PNS guide the regeneration of
cut axons
• Fibers in CNS myelinated by oligodendrocytes
do not have regenerative ability
– Oligodendrocytes inhibit regeneration of cut
central axons
Synapses
• Junction between two neurons
• Primary means by which one neuron directly interacts
with another neuron (muscle cells or glands as well)
• Anatomy of a synapse
– Presynaptic neuron – conducts action potential toward
synapse
– Synaptic knob – contains synaptic vesicles
– Synaptic vesicles – stores neurotransmitter (carries signal
across a synapse)
– Postsynaptic neuron – neuron whose action potentials are
propagated away from the synapse
– Synaptic cleft – space between the presynaptic and
postsynaptic neurons
1
Axon of
presynaptic
neuron
Synaptic knob
(presynaptic
axon terminal)
Voltage-gated
2+
Ca2+ channel Ca
Synaptic
vesicle
2
Neurotransmitter
molecule
Chemically gated
receptor-channel
for Na+, K+, or Cl–
3
Synaptic
cleft
Subsynaptic
membrane
3
4
Receptor for
neurotransmitter
5
4
5
Postsynaptic neuron
Fig. 4-15, p. 108
Axon terminal
of presynaptic
neuron
Dendrite of
postsynaptic
neuron
Synaptic
vesicles
Synaptic
cleft
Fig. 4-15, p. 108
Neurotransmitters
• Vary from synapse to synapse
• Same neurotransmitter is always released at a particular
synapse
• Quickly removed from the synaptic cleft
Synapses
Signal at synapse either excites or inhibits the postsynaptic
neuron
• Two types of synapses
– Excitatory synapses
– Inhibitory synapses
• If binding of NT opens Na+ and K+ channels the result is
a small depolarization called an excitatory postsynaptic potential (EPSP).
• EPSP brings the cell closer to threshold.
• If binding of NT opens either K+ or Cl– channels the
result is a small hyperpolarization called an inhibitory
post-synaptic potential (IPSP).
• IPSP means cell less likely to reach threshold.
Synaptic Summation
Cell body of
postsynaptic
neuron
Axon
hillock
Synaptic Summation
• Multiple EPSP and IPSP’s from numerous
synapses converge on one neuron.
• These signals can cause different changes in
the postsynaptic neuron
– Cancellation
– Spatial summation
– Temporal summation
Postsynaptic
cell
Inhibitory
presynaptic input
Postsynaptic membrane potential (mV)
Membrane
potential
recorded
(a) No (b) Temporal
summation summation
(c) Spatial
summation
(d) EPSP-IPSP
cancellation
+30
0
Excitatory
presynaptic inputs
Threshold
potential
Resting
potential
–50
–70
Time (msec)
Fig. 4-17, p. 111
Fig. 4-19, p. 109
Presynaptic
inputs
Convergence of input
(one cell is influenced
by many others)
Postsynaptic
neuron
Presynaptic
inputs
Divergence of output
(one cell influences
many others)
Postsynaptic
neurons
Arrows indicate direction in which information is being conveyed.
Fig. 4-20, p. 111
Synaptic Drug Interactions
• Possible drug actions
– Altering the synthesis, axonal transport, storage,
or release of a neurotransmitter
– Modifying neurotransmitter interaction with the
postsynaptic receptor
– Influencing neurotransmitter reuptake or
destruction
– Replacing a deficient neurotransmitter with a
substitute transmitter
Examples of drugs that alter synaptic transmission
• Cocaine
– Blocks reuptake of neurotransmitter dopamine at
presynaptic terminals
• Strychnine
– Competes with inhibitory neurotransmitter glycine
at postsynaptic receptor site
• Tetanus toxin
– Prevents release of inhibitory neurotransmitter
GABA, affecting skeletal muscles
DIRECT INTERCELLULAR COMMUNICATION
Small molecules and ions
(a) Gap junctions
(b) Transient direct linkup of cells’ surface markers
INDIRECT INTERCELLULAR COMMUNICATION VIA EXTRACELLULAR CHEMICAL MESSENGERS
Secreting cell
Local target cell
Local target cell
Electrical signal
Paracrine
(c) Paracrine secretion
Secreting cell
(neuron)
Neurotransmitter
(d) Neurotransmitter secretion
Blood
Secreting cell
(endocrine cell)
Neurohormone Blood
Electrical signal
Hormone
Distant target cell
Nontarget cell
(no receptors)
(e) Hormonal secretion
Secreting cell
(neuron)
Nontarget cell
(no receptors)
Distant target cell
(f) Neurohormone secretion
Fig. 4-20, p. 117
Chemical Messengers
Four types:
• paracrines (local chemical messengers)
• neurotransmitters (very short-range
chemical messengers released by neurons)
• hormones (long-range chemical messengers
secreted into the blood by endocrine glands)
• neurohormones (long-range chemical
messengers secreted into blood by neurons)
Hormones
• Endocrinology
– Study of homeostatic activities accomplished by
hormones
• Two distinct groups of hormones based on their
solubility properties
– Hydrophilic hormones (Proteins, peptides)
• Highly water soluble
• Low lipid solubility
– Lipophilic hormones (Steroids)
• High lipid solubility
• Poorly soluble in water
Chemical Messengers
• Extracellular chemical messengers bring about
cell responses primarily by signal transduction
– Process by which incoming signals are conveyed
to target cell’s interior
• Binding of extracellular messenger (first
messenger) to matching receptor brings about
desired intracellular response by either
– Opening or closing channels
– Activating second-messenger systems
• Activated by first messenger
• Relays message to intracellular proteins that carry out
dictated response
Fig. 4-23, p. 116
Fig. 4-24, p. 118
Fig. 4-25, p. 119
ANIMATION: Signal Transduction
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ANIMATION: Response Pathways Activated by
G-Protein-Coupled Receptors
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Blood vessel
ECF
Plasma
protein
carrier
Steroid
hormone
Plasma
membrane
Cytoplasm
Cellular response
1
9
Portion
that binds
hormone
Steroid
hormone
receptor
New
protein
8
Portion
that binds
to DNA
2
7
DNA-binding
site (active)
6
3
mRNA
5
4
DNA
Nucleus
Hormone Gene
response
element
Fig. 4-28, p. 128
Comparison of Nervous System and
Endocrine System