2. Signal Transduction Mechanisms:
Electrical Signals in Nerve Cells
 Most animals have nervous system that : 1) collects
information, 2) processes information and 3) elicits
responses to the information.
 Neurons are specially adapted for the transmission of
electrical signals.
o The cell body bears the nucleus and organelles.
o The dendrites receive (and combine) signals.
o The axons conduct signals.
o The myelin sheath surrounds the axon in a
discontinuous manner (form the nodes of Ranvier).
 Nerve cells can be long (e.g., a motor neuron's cell body
in the spinal cord and the axon ends in your toes).
 An axon ends with terminal bulbs or synaptic knobs that
transmit the signal through a specialized junction: the
synapse.

3. Membrane Potential and Action Potential
 Every cell in the body is electrically active: to a
greater or lesser degree, they all pump ions
across the cell membranes to maintain
an electrical potential difference across the
membrane.
 This difference in electrical charge between the
inside and outside of the membrane is the basis
for many types of physiological processes,
including transport of particles across the
membrane and signalling among cells.
 In some cells up to 40% of energy is used to
power active transport, a process that
maintains or restores membrane potentials.

4. Membrane potential is a property of all cells and
reflects a difference in charge on either side of the cell
membrane. Normally, cells are net negative inside the
cell which results in the resting membrane potential or
Vm (a negative resting membrane potential).

5.  The resting membrane potential depends on differing
concentrations of ions inside (cytoplasm) and
outside the membrane (extracellular fluid).
 Large negatively charged molecules (proteins, RNA)
do not pass through the membrane to set up the
negative resting membrane potential.

6.  If the cell membranes were simply permeable to these ions,
they would approach an equilibrium with equal concentrations
on each side of the membrane, and no voltage difference. But
there is a voltage difference, so the processes which produce
the membrane potential are not simply diffusion and osmosis.
 Electrical excitability depends upon “ion channels” acting like
gates for the movement of ions through the membrane to
produce an action potential.
 In passive channels, ions may freely move diffusively through
the channel. Leakage channels are the simplest type, since
their permeability is more or less constant.
 Chemically gated channels pump Na+ (and some Ca+2) out of
the cell, while pumping in K+ in the ratio of 2 K+ for every 3 Na+
pumped out.
 The flow of oppositely charged ions towards each other is the
potential or voltage. When the ions move, this is current.
 Eventually electrochemical equilibrium (chemical versus
electrical) is established and the equilibrium membrane
potential is reached.

7. Sodium-Potassium Pump

8.  Nerve, muscles and some glands share electrical
excitability which, in response to stimuli, causes
rapid changes in membrane potential (action
potential) to occur.
 Within a millisecond, the membrane potential
changes from negative to positive and back.
 In neurons, the action potential moves down the axon
as a nerve impulse.

9.  Steady-state movement
of ions define the
membrane potential and
is maintained by the Na+-
K+ pump.
 In the resting state of a
neuron, the inside of the
nerve cell membrane is
negative with respect to
the outside. The voltage
arises from differences
in concentration of the
K+ and Na+ ions.
 Depolarization (or a
lowering of the
membrane potential)
results from flow of
positive sodium ions into
the cell.

10.  In nerve cells, a neurotransmitter can affect the activity of
a postsynaptic cell via 2 different types of receptor proteins:
ionitropic or ligand-gated ion channels, and metabotropic receptors.
1. Ligand-gated ion channels combine receptor and channel
functions in a single protein complex.
2. Metabotropic receptors usually activate G-proteins, which
modulate ion channels directly or indirectly through intracellular
effector enzymes and 2nd messengers.

11.  Voltage-gated ion channels respond to differences in
voltage across the membrane (ligand-gated ion channels
respond to ligands).
 Specific domains of voltage-gated channels act as
sensors and inactivators.
 A specific transmembrane stretch of amino acids act as
voltage sensor.
 Based upon the conformation of the voltage-gated
sodium channel, the channel can be closed but sensitive
to a depolarizing signal (channel gating) or completely
desensitized to the signal (channel inactivation) by the
inactivating particle, a stopper-like part of the channel
protein itself.
 Recovery from an action potential is partly dependent on
a type of voltage-gated K+ channel which is closed at the
resting voltage level but opens as a consequence of the
large voltage change produced during the action
potential.

12. Voltage-gated Ion
Channels

13.  The resting
potential of a
neuron is -70 to -80
mV.
 Action potentials
propagate electrical
signals along an
axon. Initially, a
resting neuron is
made ready for
electrical activity
through the balance
of ion gradients and
membrane
permeabilities.  More depolarization causes the membrane to
 A small amount of reach the threshold potential at which the nerve
depolarization cell membrane rapidly changes electrical
(<+20mV) will properties and ion permeability to initiate an
normally result in action potential.
recovery without  The action potential is a brief depolarization/
effect. repolarization that propagates from the site of
origin.

14.  Graded potentials
are short lived
Graded Potentials
depolarizations or
hyperpolarizations
of an area of
membrane.
 These changes
cause local flows of
current that
decrease with
distance.
 The more intense
the stimulus, the
more ion channels
that are opened,
and the greater the
voltage change.

16.  The action potential results from the rapid
movement of ions through axonal membrane
channels and the increased sodium current results
in a positive feedback loop known as the Hodgkin
cycle.
 Sub-threshold depolarization results in no action
potential generated, which is at least partially due to
the outward movement of K+ ions. If the K+ ion exit
cannot compensate for the influx of Na+ ions, the
membrane reaches the threshold of depolarization.
 When the voltage-dependent Na+ channels open, Na+
flows in during the depolarizing phase.
 Once the membrane potential peaks, the
repolarizing phase begins with the inactivation of
the Na+ channels (blocking the Hodgkin cycle) and
the opening of the voltage-gated K+ channels.

17.  The recovery is due to the passive movement of
ions- not the action of the Na+/K+ pumps.
 During the absolute refractory period (~few
milliseconds), Na+ channels cannot be opened by
depolarization and no action potential can be
generated.
 During the hyperpolarizing phase, the Na+channels
are reactivated but Na+ flow is opposed by K+
currents which produces a relative refractory
period.

18. 1.The passive spread of
Action potentials are propagated
depolarization causes
along the axon without losing cations (mostly K+) to
strength by active propagation: spread to adjacent
regions of the axon's
cytoplasm.
2.As the depolarization
spreads, it loses its
magnitude and MUST
be actively propagated
to move far.
3.Propagation depends
upon the passive
spread of depolariza-
tion to induce the
membrane potential in
adjacent parts of the
axon to reach the
threshold potential
which then triggers the
intake of Na+ ions and
continuation of the
cycle.

19. For example, signals move from the dendrites 4.At the axon hillock, a
through the cell body to the base of the axon great influx of Na+
(the axon hillock) where Na+ channels are ions can occur which
concentrated. specify that action
potentials initiated
here are propagated
down the axon. The
propagated action
potential is the nerve
impulse.
5.The rate of impulse
transmission depends
on electrical
properties of the
axon such as the
electrical resistance
of the cytosol and the
ability to retain
electric charge
(capacitance) of the
plasma membrane.

20.  The hyperpolarizing phase results from the
increased permeability of K+ due to the open
voltage-gated K+ channels. The membrane
potential returns to resting state with the closing
of the voltage-gated K+ channels.
 Hyperpolarization prevents the neuron from
receiving another stimulus during this time, or at
least raises the threshold for any new stimulus.
 Hyperpolarization also prevents any stimulus
already sent up an axon from triggering another
action potential in the opposite direction. It
assures that the signal is proceeding in one
direction.
 After hyperpolarization, the Na+/K+ pump
eventually brings the membrane back to its
resting state of -70 mV .

21.  The discontinuous myelin
sheath acts like an electrical
insulator surrounding the axon.
 The neurons of the CNS have
myelin sheath composed of
oligodendrocytes and in the
PNS the myelin sheath is
composed of Schwann cells. In
each case, the myelin cells
wrap several layers of their
plasma membranes around the
axon.
 Each Schwann cell surrounds a
stretch of 1 mm of axon, with
many Schwann cells acting to
insulate each axon.

22.  Myelination permits a
depolarization of events to
spread farther and faster
than without because of
saltatory propagation.
 This process depends
upon the gathering of
voltage-gated sodium
channels at the nodes of
Ranvier.
 Action potentials jump
from node to node
(saltatory propagation)
which is very rapid when
compared to propagation
in neurons that have the
myelin removed.

23. SYNAPSE
Synapses are specialized junctions through which
NS cells signal to one another and to effectors
(muscles or glands). They provide the means through
which the NS connects to and controls the other
systems of the body.

24. Nerve cells communicate with muscles, glands
and other nerve cells via synaptic
transmission. In an electrical synapse, the axon
of the presynaptic neuron connects to the
dendrite of postsynaptic neuron by gap
junctions.

25. In a chemical synapse, the presynaptic
and postsynaptic neurons are
separated by a gap, the synaptic cleft.

26. A NEUROTRANSMITTER is a small molecule that, through
the interaction with a specific receptor, relays a signal
across nerve synapses. Neurotransmitter molecules that
are kept in the terminal bulbs or synaptic knobs are
secreted into the synaptic cleft and then bind to receptors
in the postsynaptic neuron. This generates an electrical
signal to stimulate or inhibit a new action potential.

27. A neurotransmitter must: 1) cause a response
when injected into the synaptic cleft, 2) occur naturally
in the presynaptic neurons and 3) be released when the
presynaptic neurons are stimulated.
An
An inhibitory
excitatory neuro-
neuro- transmitter
transmitter causes
causes hyperpola-
depolari- rization in
zation the post-
synaptic
neuron.

28.  Neurons can integrate both excitatory and inhibitory
signals from other neurons.
 The summation of synaptic inputs leads to whether
or not an action potential is formed in the
postsynaptic neuron.

29.  Acetylcholine is the most common neurotransmitter in
vertebrate outside of the CNS to form cholinergic synapses
between PNS neurons and at neuromuscular junctions.
 The catecholamines (dopamine, norepinephrine, epinephrine: all
tyrosine derivatives) are found in adrenergic synapses at
junctions between nerves and smooth muscles and nerve-nerve
junctions in the brain.
 Other neurotransmitters are other amino acids and
derivatives (histamine, serotonin, gamma-aminobutyric acid
[GABA], glycine, glutamate). Serotonin functions as an
excitatory neurotransmitter in the CNS by indirectly closing the
K+ channels.
 The neuropeptides are short chains of amino acids formed by
cleavage of precursor proteins and stored in secretory vesicles.
 The enkephalins are neuropeptides that are produced in the
brain to inhibit pain reception.
 The neuropeptide endocrine hormones (prolactin, growth
hormones and leutinizing hormone) act on tissues other than the
brain.

30.  Elevated calcium levels stimulate
secretion of neurotransmitters from
the presynaptic neurons.
 The neurotransmitters are stored in
neurosecretory vesicles in the
terminal bulbs.
 The release of calcium within the
terminal bulb mobilizes
neurosecretory vesicles rapidly (by
the phosphorylation of synapsin and
release from the cytoskeleton) and
causes the fusion of the vesicles to
the plasma membrane and
neurotransmitters release.
 Exocytosis of neurotransmitters
requires the docking and fusion of
vesicles with the plasma membrane
requires ATP and voltage-gated
calcium channels.

31.  When the action potential
reaches the ends of the
axon, voltage-gated calcium
channels open and calcium
flood in.
 This initiates the docking of
the vesicles at the
presynaptic neuron's
membrane in an active zone
through the action of
docking proteins
(synaptotagamin,
synaptobrevin, syntaxin).
 The docking process is
blocked by neurotoxins such
as tetanus toxin (in the spinal
cord) and botulinum toxin (in
the motor neurons).

32. Neurotransmitters are detected by specific receptors on
postsynatic neurons such as ligand-gated
channels.The acetylcholine receptor is a ligand-gated
sodium channel that binds two molecules of acetylcholine
to open. This receptor is specifically bound by snake venom
components (alpha-bungarotoxin and cobratoxin).

33.  The GABA (gamma-aminobutyric acid) receptor is a
ligand-gated Cl- channel which produces an influx of Cl-
ions in the postsynaptic neuron.
 The entry of Cl- ions neutralize the effect of Na+ influx
on the membrane potential which reduces
depolarization and may prevent initiation of an action
potential in the postsynaptic neuron.
 Benzodiazeprine drugs (Valium and Librium) enhance
the effects of GABA on the receptor to produce a
tranquilizing effect.
 For neurotransmitters to work effectively and not
overstimulate or inhibit, they must be neutralized shortly
after their release by either degradation or recovery by
the presynaptic neuron.
 Acetylcholine is hydrolyzed by acetylcholinesterase.
 Some neurotransmitters are returned to the presynaptic
axon terminal bulbs by specific transporter proteins
(endocytosis).

38. Brain images showing decreased dopamine (D2) receptors in the brain
of a person addicted to cocaine versus a nondrug user. The dopamine
system is important for conditioning and motivation, and alterations such
as this are likely responsible, in part, for the diminished sensitivity to
natural rewards that develops with addiction.

39. http://www.the-
aps.org/education/itip/im
ages/membranepotenstu.
pdf
http://www.rwc.uc.edu/ko
ehler/biophys/4c.html
http://hyperphysics.phy-
astr.gsu.edu/hbase/biolo
gy/mempot.html
http://www.mun.ca/biolog
y/desmid/brian/BIOL2060
/BIOL2060-13/CB13.html
http://en.wikipedia.org/wi
ki/Membrane_potential