Neurophysiology Part 1

 Contents:
• Neurophysiology
– Nervous System Overview
– Electrical Communication in Neurons
– Chemical Communication in Neurons
 Session Objectives
At the end of this session students will be able to:

 Understand the basic concept of bioelectric signals Includes

 Graded potential
 Action potential

 Explain the generation and propagation of information transfer

between cells and tissues
 The Nervous System
• The Nervous System is the master controlling and
communication system of the body, specialized to
quickly detect and respond to stimuli.
• It is composed of:
• Central Nervous System (brain, spinal cord)
– Integration
• Peripheral Nervous System (peripheral nerves and
receptors).
– Afferent Division (Sensory information IN)
– Efferent Division (Motor responses OUT)
 Central nervous system
(CNS)
Brain and
Input Output
spinal
to CNS from
cord
from CNS to
peripher peripher
y y
Peripheral
nervous
system (PNS)
Afferent Efferent
division division

Stimuli in
Sensor Visceral Somatic Autonomic digestive
y stimuli nervous nervous tract
stimuli system system

Motor Sympathetic Parasympatheti Enteric

neurons nervous c nervous
system nervous system system

KEY

Central nervous system Smooth muscle Digestive

Skeletal
Peripheral nervous Cardiac muscle organs
muscle
system
Afferent division of PNS* Exocrine glands only
s
Efferent division of PNS Some
endocrine
Somatic nervous system
glands
Autonomic nervous
system
Enteric nervous Effector organs
(made up of muscle and gland tissue) Fig. 5-1, p.
system*
Nervous System Functions

• Functions:
– Electrical & Chemical Communication
– Sensory Input
– Integration
– Motor Output
 Central Peripheral
nervous nervous
system system
(spinal cord)
Cell
Axon body Afferent neuron
terminal
s

Central Peripheral
Sensory
axon axon
recepto
(afferent fiber)
r

Interneuro
n

Efferent
neuron* Effector organ
(muscle or
Axon gland)
(efferent Axon
Cell fiber)
body terminal
s
* Efferent autonomic nerve pathways consist of a two-neuron chain
between Fig. 5-2, p.
 Nervous System Organization
• PERIPHERAL RECEPTORS sense information from the body
• PERIPHERAL SENSORY NERVES bring in sensory information to the spinal cord
and/or brain
• The SPINAL CORD either relays sensory information to the brain (OR it can
reflexively integrate and respond on its own).
• The BRAIN has specialized regions to process and integrate sensory
information and decide how to respond
• The brain sends motor commands out through the SPINAL CORD (OR directly
through cranial nerves to muscles, organs and glands).
• PERIPHERAL MOTOR NERVES carry motor commands to muscles, organs, and
glands
• The muscles, organs, and glands are the Peripheral Effectors, which carry out
a motor response
Nervous System Cells
• There are two major cell categories in the
nervous system: neurons and neuroglia
• Neurons are the primary signaling and
communicating cells
• Neuroglia are supportive cells that help with
neuron development, growth, survival and
structural support
• ependymal cells
• astrocytes
• schwann cells
• oligodendrocytes
• microglia
 Nervous System Cells
Space containing
cerebrospinal
fluid

Ependymal
cell
Brain
interstitia Neurons
l
fluid

Astrocyte

Oligodendrocyt Capillar
e y

Microgli
a

Fig. 5-3, p.
Table 5-1 p138
Neurons
• Neurons are the primary signaling and communicating cells
in the nervous system
• They are large branching cells that connect nervous system
pathways electrically and chemically
• They come in many shapes and sizes, but in general are
composed of:
• dendrites
• cell body
• axon hillock
• axon
• axon terminals
 Neuron Structure
Neuron structure reflects its function in stimulus response
and communication
• dendrites: receive input from other cells or receptors
• cell body: contains the nucleus
• axon hillock: integrates electrical input from dendrites,
highly excitable region
• axon: transmits electrical input to the axon terminal
• axon terminals: end of the axon, contacts the next cell and
releases chemical neurotransmitters
 1) Input zone receives incoming
signals from other neurons.
Dendrites

Cell body
2) Trigger zone
initiates action 3) Conducting zone conducts
potentials. action potentials in undiminishing
Nucleus fashion, often over long distances.
Axon hillock
Axon (may be from 1mm
to more than 1 m long)

Axon
terminals
Dendrites 4) Output zone releases
neurotransmitter that
Cell body influences other cells.

Axon

Fig. 4-8, p. 98
 Synapses

Neurons are connected to other cells by synapses, specialized

regions of contact
1.Synapse: neuron-neuron connection
2.Neuromuscular Junction: neuron- skeletal muscle
connection
3.Neuro-Glandular Synapses: neuron-gland synapse
 Neuron Communication
Neurons communicate electrically through
 electrical gradients and
 chemically through neurotransmitters
• electrical communication: movement of ions in an out of
cell membranes
• can be small, local or travel long distances down the branches
of the cell
• chemical communication: release of neurotransmitters
(ligand) to nearby neurotransmitter receptors (receptor)
at synapses
 Stimuli Activate Neurons
• Neurons are excitable, and are activated by stimuli to send
signals to other cells
• stimulus: a stimulus is any change in the environment that
triggers a change in the neuron
– mechanical (touch, vibration, movement)
– electrical (ion, voltage changes)
– chemical (taste, smell, ligands from other cells)
• Activation happens through activation of channels on dendrites
– stimulus comes in and changes the shape of the channel, the channel
then transmits via electrical and/or chemical changes inside the cell.
 Types of Ion Channels found in Neurons
• Mechanically gated channels – open in response to physical forces
• Voltage-gated channels – open or close in response to changes in electrical
membrane potential.
• Ligand-gated channels – chemically gated, open when chemicals or
neurotransmitters bind.
• Leaky channels – always open, non-gated
 Electrical Communication

• electrical communication within a neuron occurs by

movement of ions in and out of the membrane
• ions carry electrical charge
• different concentrations of ions at the cell membrane
create electrical gradients
• electrical gradients are measured as membrane
potential
 Membrane Potential
• Membrane potential is defined as the amount of electrical charge
present on the inside of the cell (ICF) compared to the outside of
the cell membrane (ECF).
• POSITIVE membrane potential: the inside of the cell is more
positive than the outside of the cell
• more positive ions (ex: K+) inside the cell than outside the cell
• OR that there are more negative ions (ex: Cl-)outside the cell
• NEGATIVE membrane potential: the inside of the cell is less
positive than the outside of the cell
• means there are more negative ions inside the cell (ex: Cl-) than outside
the cell
• OR that there are more positive ions (ex: Na+) outside the cell.
 Membrane Potential
• Membrane potential is measured in electrical Volts, but is very small, so mV
(millivolts 1/1000 Volt) is more appropriate
• To calculate the membrane potential, sum the amount of positive and
negative charge inside the cell vs. outside the cell
– EXAMPLE: membrane potential = 0mV
• inside: +10, -10
• outside: +10, -10 and
• SUM: no difference across the membrane, charge equilibrium
– EXAMPLE: membrane potential = -10mV
– inside: +5, -10
– outside: +15, -10
– a difference of -10 mV across the membrane, inside is less positive (more
negative)
– the charged ions will accumulate at the membrane due to this electrical
gradient, but cannot pass without channels
 0 mV Membrane Potential
Membrane
OUT IN

(10+, 10–) (10+, 10–)

(a) Membrane has no potential

Fig. 3-19a, p.
 -10 mV Membrane Potential
OUT IN

(15+, 10–) (5+, 10–)

(b) Membrane has potential

Fig. 3-19b, p.
 -10 mV Membrane Potential: Ion
Accumulation at Membrane
OUT IN

Remainder of Separated charges Remainder of

fluid electrically fluid electrically
neutral neutral

(c) Separated charges responsible for potential

Fig. 3-19c, p.
 Ion Accumulation at Membrane

• When an electrical gradient is present at the membrane, the

ions will accumulate very close to the membrane on either
side due to the attraction of negative charge to positive charge
• BUT remember: ions (polar) cannot pass through the lipid
bilayer (large hydrophobic region) without the help of channels
• Electrical energy is now being stored very locally at the cell
membrane, waiting for a signal to change
 Ion Accumulation at Membrane

Plasma membrane

d) Separated charges forming a layer along plasma membrane

Fig. 3-19d, p.
 Magnitude of Membrane Potential
• Increasing the number of ions that accumulate at the membrane
increases the magnitude of the membrane potential.
A B C

(e) Magnitude of potential membrane B has more potential than

membrane A and less potential than membrane C

Fig. 3-19e, p.
 Unequal Distribution of Ions
• ECF rich in Na+ ions and chloride ions (Cl-).
• In cytosol, the main cation is K+ and two dominant anions are
phosphates attached to ATP and amino acids in proteins.
• Plasma membrane has more K+ leakage channels than Na+ leakage
channels.
• The number of K+ that diffuse down their concentration gradient out
of cell into ECF is greater than number of Na+ that diffuse down their
concentration gradient from the ECF into the cell.
• As more and more positive K+ exit, inside of the membrane
becomes increasingly negative and outside of the membrane
becomes increasingly positive.
Resting Membrane Potential
Concentration gradient of ions
 Membrane Potential in Neurons
• Overall, neurons have NEGATIVE MEMBRANE POTENTIAL at
rest this is due to 3 main factors:
• Proteins (A-) inside
• Inside a neuron, there are many negative molecules (A-) this is due
to large number of negatively charged proteins
• Potassium (K+) inside
• A moderate level of K+ inside the membrane
• Sodium (Na+) outside
• High Na+ outside the membrane
MEMBRANE POTENTIAL (resting neuron) = -70mV
 Membrane Potential Values
• Taking into account the A- , Na+ and K+, a general
neuron has a membrane potential of -70mV when
no electrical signaling is occurring, this is resting
membrane potential
+35 mV
• All changes in membrane potential due to signaling

depolarization
are now compared to REST 0 mV
• The proteins do not generally change, so we mainly
focus on the ion (Na+ and K+) changes: -35 mV

• When + ions move INTO the cell, the membrane -70 mV REST
potential will become more positive, this is

hyperpolarization
called depolarization -105 mV
• Then + ions move OUT of the cell, the
membrane potential will become less positive
(more negative), this is called
hyperpolarization.
 Forces on Ion Movement
• The Na+ and K+ ions are affected by electrical gradients and their
individual concentration gradients
• FORCES on K+ (inside):
• concentration gradient: K+ wants to move OUT of the cell
• electrical gradient: the negative membrane potential wants to keep K+ IN the
cell
• If these could balance out, equilibrium for K+ is reached, this is at -90mV
• FORCES on Na+ (outside):
• concentration gradient: Na+ wants to move IN to the cell
• electrical gradient: the negative membrane potential pulls Na+ IN to the cell
• IF these could balance out, equilibrium for Na+ is reached, this is at +60mV
• BUT NOTHING MOVES WITHOUT CHANNELS
 Plasma membrane

ECF ICF

Concentration
gradient for K+

Electrical
gradient for K+

EK+ = –90 mV Fig. 3-20, p.

 Plasma membrane

ECF ICF

Concentration
gradient for Na+

Electrical
gradient for Na+

ECF
anions,
mostly

ENa+ = +60 mV Fig. 3-21, p.

 Na+ and K+ Channels at rest
• The movement of ions will be determined by the type of
ion channels that are present.
• At rest:
• K+ channels:
– leaky K+ channels: when the neuron is at rest: passive, open K+
channels allow K+ to leak out of the cell, nearing it equilibrium.
– K+ permeability at rest is high, but not complete
• Na+ channels:
– when the neuron is at rest: there are very few open Na+
channels
– Na+ permeability at rest is low, very far from its equilibrium
 Forces Driving Ion Movement
Relatively
ECF ICF large net
diffusion of
K+ outward
establishes
an EK+ of –90
mV

No diffusion
of A– across
membrane

Relatively
small net
diffusion of
Na+ inward
and associated neutralizes
some of the
potential
created by
K+ alone
Resting membrane potential = –70 mV
Fig. 3-22, p.
 Electrical Signaling in Neurons
• Now that we have established the storage of electrical
membrane potential at rest in Neurons, lets take a look
at how it is USED to actively signal within the nervous
system
• Electrical signaling in neurons takes place by changing
membrane potential away from rest
• This is done by opening or closing specific channels to
allow ions to move in or out of the cell, due to a
TRIGGER event.
• This causes changes in the cell, such as neurotransmitter
release that can be read by other cells
 Electrical Signaling in Neurons
Electrical Signaling Terms
• Membrane Potential: the difference in electrical charge
across the cell membrane, measure in mV
• Polarization: separation of charge across the membrane
(example: -70mV at rest in neurons)
• Depolarization: membrane becomes less polarized (example:
positive ions move IN in neurons)
• Repolarization: membrane potential returns to its resting
value after signaling complete
• Hyperpolarization: membrane becomes more polarized
(example: positive ions move OUT in neurons)
 4

Na+ channel closes and is inactivated K+ channel opens

(activation gate still open; inactivation (activation gate opens)
gate closes)

Na+ channel
reset to closed
but capable
Na+ channel of opening K+ channel
opens and (activation closes
is activated gate closes; (activation
inactivation gate closes)

ase
(activation
gate opens; gate opens)

Na+ in → rising ph

K+ out → fa
inactivation
gate already
open)
3 5

llin
g p h a se
K+ voltage-gated channel closed
(activation gate closed)
2
Threshold potential

1 6
Resting potential 8
7
Depolarizing
triggering event

Na+ voltage-gated channel closed Stepped Art

(activation gate closed; inactivation gate open)
Fig. 4-7a, p. 96
 Membrane Potential at Rest
(membrane is polarized)
Extracellular fluid
Closed channels Unbalanced charges
distributed across the
plasma membrane that
are responsible for
Portion of Intracellular fluid membrane potential
an excitable
cell

(a) Entire membrane at resting potential

Fig. 4-2a, p. 92
 Membrane Potential changes
+20
+10 Depolarization (decrease in potential;
Membrane potential (mV) 0 membrane less negative)
–10
Repolarization (return to resting potential
–20
after depolarization)
–30
–40 Hyperpolarization (increase in
–50 potential; membrane more negative)
–60
–70 Resting potential
–80
–90

Time (msec)

Fig. 4-1, p. 90
 Electrical Signaling Types
• There are two main ways that membrane potential changes
in neurons:
• Graded Potential: a small, local change in membrane
potential that can vary in size, and does not travel far
• caused by small changes in nearby connected cells or receptors
• used for fine-tuned information, can build up to become a larger
trigger
• Action Potential: a large, fast, long distance spread of
membrane potential change that is the same magnitude
every time it occurs
• caused by large changes and/or multiple connecting cells or
receptors changing
• all or none signal to communicate on/off triggers between cells
 Graded Potentials
• Graded Potentials:
• small, local membrane potential changes due to a triggering
event
• gated ion channels open for a short time in a small section
of the membrane
• ion specific to that channel moves passively with its gradient
• local current flows change membrane potential in a small
area, but signal is dissipated with distance from gated ion
channels that first open
• Excitatory: positive ions move IN (example: Na+)
• Inhibitory: negative ions move IN (example Cl-), or positive
ions move OUT (example K+)
 Graded Potentials
Triggering event opens ion channels, most commonly permitting net Na+ entry

Inactive area Active area depolarized Inactive area

at resting potential (a graded potential) at resting potential
(b) Inward movement of Na+ depolarizes membrane, producing a graded potential

Fig. 4-2b, p. 92
Graded Potentials Dissipate
Current flows between the active and adjacent inactive areas

Inactive Previously Original Previously Inactive

area inactive area active area inactive area area
being depolarized being depolarized
Spread of depolarization

(c) Depolarization spreads by local current flow to adjacent inactive

areas, away from point of origin

Fig. 4-2c, p. 92
 Action Potentials
• Action Potentials:
• a large, fast, long distance spread of membrane potential change
• graded potentials build up until a threshold is reached in the cell
• starts at one triggered site, but is propagated down the entire
cell without dissipating
• the same magnitude every time it occurs (All or none)
• the same exact pattern of membrane potential changes every
time it occurs
• one-way propogation down the axon toward the synaptic
terminal
Action Potential Pattern
• Once triggered, an action potential has the exact
same pattern every time it occurs:
1. REST: Membrane Starts at rest
2. THRESHOLD: Threshold reached?
3. RISING PHASE: Depolarization
4. FALLING PHASE: Repolarization
5. DIP: Hyperpolarization
6. Return to Rest
 +70
+60
+50
+40
+30

Membrane potential (mV)

+20
+10 Action potential
0
–10
20
–30
–40
–50 Threshold potential
–60
–70 Resting potential
–80
After hyperpolarization
–90

Time (msec)
1 msec
Slow depolarization
to threshold Fig. 4-4, p. 94
Voltage Gated Channels
• Action potential events are caused by the opening
and closing of Na+ and K+ channels that are
sensitive to membrane potential changes (voltage
gated). Each has a specific pattern and timing.
• Voltage Gated Na+ channels:
• closed at -70mV (rest)
• gate opens open rapidly at -50 to -55mV
• closes by separate inactivation gate
• Voltage Gated K+ channels:
• closed at -70mV (rest)
• gate opens slowly at -50 to -55 mV
• gate closes slowly
VOLTAGE-GATED SODIUM CHANNEL VOLTAGE-GATED POTASSIUM CHANNEL
Activation
gate
ECF

Plasma
membrane

ICF Rapid Slow Delayed

Activation gate opening closing opening
triggered triggered triggered
Inactivation gate at threshold at threshold at threshold
(a) Closed but (b) Open (c) Closed and not (d) Closed (e) Open
capable of opening (activated) capable of opening
(inactivated)

Fig. 4-5, p. 95
Action Potential Events: REST
REST: Membrane Starts at rest
• -70 mV
• Due to A-, K+ and Na+ gradients, Na/K
pump
• K+ leaky channels open
• Na+ voltage gated channels closed
• K+ voltage gated channels closed
Action Potential Events: THRESHOLD
THRESHOLD: Threshold reached?
• -50 to -55 mV
• Due to build up of triggering events
(graded potentials!) and a combination
of ions moving, depending on the input
to the cell

SIGNAL IS TURNED ON
Action Potential Events: RISING PHASE
RISING PHASE: Depolarization
• moves DOWN
• Due to Na+ rushing in
• K+ leaky channels open
• Na+ voltage gated channels open
• K+ voltage gated channels closed

Na+ RUSHES IN
Action Potential Events: FALLING PHASE & DIP
FALLING PHASE: Repolarization
• moves down toward -70
• DUE to K+ moving out
• K+ leaky channels open
• Na+ voltage gated channels inactive
• K+ voltage gated channels open
DIP: Hyperpolarization
• moves toward -90
• K+ voltage gated channels continue to stay
open past resting membrane potential
K+ MOVES OUT
 Action Potential Events: Final Rest
Return to Rest:
• the Na/K pump re-estabilishes the original gradients
• K+ leaky channels open
• Na+ voltage gated channels closed, ready again
• K+ voltage gated channels closed
 4

Na+ channel closes and is inactivated K+ channel opens

(activation gate still open; inactivation (activation gate opens)
gate closes)

Na+ channel
reset to closed
but capable
Na+ channel of opening K+ channel
opens and (activation closes
is activated gate closes; (activation
inactivation gate closes)

ase
(activation
gate opens; gate opens)

Na+ in → rising ph

K+ out → fa
inactivation
gate already
open)
3 5

llin
g p h a se
K+ voltage-gated channel closed
(activation gate closed)
2
Threshold potential

1 6
Resting potential 8
7
Depolarizing
triggering event

Na+ voltage-gated channel closed Stepped Art

(activation gate closed; inactivation gate open)
Fig. 4-7a, p. 96
 Action Potential Refractory Periods
Action potential timing is key for electrical signaling, so the
overlap of actions potentials is limited by two refractory
periods
Absolute Refractory Period: NO other action potentials can
occur during this time because Na+ channels are either
maximally open or inactive
• during rising phase and repolarization
Relative Refractory Period: another action potential can only
occur if the triggering stimulus is very large because only a
few Na+ channels are available and K+ is exiting the cell,
opposing depolarization triggers that may come in.
• during dip phase (“after hyperpolarization”)
 Absolute Relative
refractory refractory
period period

resting Na+ permeability)

(times more permeable than
Relative membrane permeability
Membrane potential (mV) +3
Action potential 600
0

0 Na+ permeability

300

K+ permeability

–70
25
1
1 2 3 4 5 6 7 8
Time (msec) Fig. 4-11, p.
 Graded Potentials are Input to the Dendrites

• The dendrites receive multiple inputs from other cells or

receptors, causing multiple graded potentials to build up and
excite the cell.
• If enough excitatory input is received, threshold is reached at the
axon hillock
• The action potential will then travel down the axon to the axon
terminal.
 1) Input zone receives incoming
signals from other neurons.
Dendrites

Cell body
2) Trigger zone
initiates action 3) Conducting zone conducts
potentials. action potentials in undiminishing
Nucleus fashion, often over long distances.
Axon hillock
Axon (may be from 1mm
to more than 1 m long)

Axon
terminals
Dendrites 4) Output zone releases
neurotransmitter that
Cell body influences other cells.

Axon

Fig. 4-8, p. 98
 Action Potential Propogation
Action potentials spread in an ALL or NONE fashion down the
axon once they are triggered at the axon hillock
• Once a group of Na+ voltage gated channels reaches threshold,
Na+ rushes in, bringing successive patches of membrane to
threshold, and creating of opening more Na+ voltage gated
channels
Action potentials ONLY move in one direction, down the axon
toward the axon terminal. Due to temporary inactivation of
Na+ voltage gated channels
 Adjacent inactive area into
Active area at which depolarization is
peak of action spreading; will soon reach Remainder of axon
potential threshold still at resting potential

Graded Local current flow that depolarizes

potential adjacent inactive area from resting
> threshold
potential to threshold potential

Direction of propagation of action potential

Fig. 4-9a, p.
 Adjacent area
that was
brought to New adjacent
Previous active threshold by inactive area
area returned local current into which
to resting flow; now depolarization is
potential; no active at peak spreading; will soon
longer active; in of action reach threshold Remainder of axon
refractory period potential still at resting potential

Fig. 4-9b, p.
 New adjacent inactive area
Previous active New active area into which depolarization
area returned to at peak of action is spreading; will soon reach
resting potential potential threshold

“Backward” current “Forward” current flow excites

flow does not reexcite new inactive area
previously active area
Direction of propagation
because this area is
of action potential
in its refractory period
Fig. 4-10, p.
Factors Influencing Action Potentials
How fast an action potential can travel down an axon is
called the conduction velocity. There are a two main
factors that can influence conduction velocity:
1. Myelination: increased myelin insulation, increases the
speed of conduction
2. Axon diameter: large diameter axons have fast
conduction
 Myelination & Saltatory Conduction
Myelination: myelin is a thick lipid-rich layer that is formed by
oligodendrocytes (CNS) or Schwann cells (PNS)
• up to 300 layers thick, insulates the axons
• no ion channels or ion flow under myelin
• discontinuous chunks of myelin, with spaces between (Nodes of Ranvier)
Saltatory Conduction: myelination allows this fast, efficient
conduction to take place in axons
• ions and electrical charge only move at Nodes of Ranvier
• voltage gated Na+ and K+ channels concentrated at Nodes of Ranvier
• increases efficiency, fewer Na/K pumps needed
• electrical potential jumps from node to node, increasing the speed of
conduction
 Nodes of Ranvier Myelin sheath

Myelin
sheath
Axon
Axon of neuron
Plasma
membrane

(a) Myelinated fiber

Fig. 4-12a, p. 103
 Axon

Cytoplasm
Nucleus
Schwann cell

Node of Ranvier

(b) Schwann cells in peripheral nervous system

Fig. 4-12b, p. 103
 Myelin sheath Axon

Nodes of Oligodendrocyte
Ranvier

(c) Oligodendrocytes in central nervous system

Fig. 4-12c, p. 103

 Adjacent inactive node
into which depolarization
Active node at peak is spreading; will soon Remainder of nodes
of action potential reach threshold 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

 Adjacent node that was New adjacent inactive
Previous active node brought to threshold by node into which
returned to resting local current flow now depolarization is
potential; no longer active at peak of action spreading; will soon
active potential reach threshold

Fig. 4-13, p. 104

 Axon Diameter
Axon Diameter: the width of the axon determines the resistance
to electrical current flow
Large diameter axons: low resistance, fast conduction
• up to 120 meters/second (268 mph)
• example: neuron to skeletal muscle
Small diameter axons: high resistance, slower conduction
• as low as 0.7 meters/second (2 mph)
• example: neuron to digestive organs
• NOTE: Space is limited, so if an axon needs to have fast
transmission, it will be both large diameter and myelinated
The End