+

Cell communication and transport

excitability, action potential, and transport
Juan Zhen, Ph.D
Chapter 8

+
Outline

Cell membranes and transport

Tonicity vs Osmolarity

Electrical signals in neurons

Action potential Na, K

channel

Cell to cell communication

Integration of neuronal
information transfer

Anatomy of Neurons, glia cells

and synapses

+
Cell membrane and transport

+
Functions of Membrane Proteins

Structural proteins

Enzymes

Membrane receptor proteins

Transporters

Pumps

Channel proteins

Carrier proteins

Figure 3.2b ESSENTIALS The Cell Membrane

The Fluid Mosaic Model of Biological Membranes

Glycoprotein

Peripheral proteins
can be removed
without disrupting
the integrity of the
membrane.

This membraneTransmembrane
spanning protein
proteins cross the
crosses
the membrane
lipid bilayer.
seven times.
Carbohydrate

Phospholipid heads
face the aqueous
intracellular and
extracellular
compartments.
Lipid tails
form the
interior
layer of the
membrane.

COOH

Lipid-anchored
proteins
Cytoplasm

Cholesterol molecules insert

themselves into the lipid layer.

Extracellular
fluid

Peripheral
protein

Cytoskeleton
proteins.
Cell Intracellular NH
2
membrane fluid

Phosphate
Cytoplasmic loop

ENERGY REQUIREMENTS

Uses energy of
molecular motion.
Does not require ATP

MEMBRANE TRANSPORT

Requires energy
from ATP

Diffusion
Endocytosis

Simple
diffusion

Molecule
goes through
lipid bilayer

Facilitated
diffusion

creates
Secondary
Primary
concentration
active
active
gradient
transport
transport
for

Mediated transport
requires a
membrane protein

Exocytosis
Phagocytosis

Uses a
membrane-bound
vesicle

PHYSICAL REQUIREMENTS

Figure 5.5

Figure 5.7 Ficks law of diffusion

Extracellular fluid
Membrane
surface area

Lipid
solubility

Molecular
size

Concentration
outside cell

Concentration
gradient
Composition
of lipid layer

Intracellular fluid

Factors affecting rate of diffusion

through a cell membrane:
Lipid solubility
Molecular size
Concentration gradient
Membrane surface area
Composition of lipid layer

Concentration
inside cell

Ficks Law of Diffusion

Rate of diffusion surface area concentration gradient membrane permeability

Membrane Permeability

Membrane permeability

lipid solubility
molecular size

Changing the composition of the lipid layer can

increase or decrease membrane permeability.

Figure 5.13 Facilitated diffusion of glucose into cells

High glucose
concentration

GLUT

[Glucose]out

[Glucose]in

high[Glucose]out

[Glucose]in
stays low

ATP
ADP

Glycogen
Low glucose
concentration

Facilitated diffusion brings glucose

into the cell down its concentration
gradient.

G-6-P

Glycolysis

Diffusion reaches equilibrium when the

glucose concentrations inside and
outside the cell are equal.

Conversion of imported glucose into

glucose 6-phosphate (G-6-P) keeps
intracellular glucose concentrations
low so that diffusion never reaches
equilibrium.

Table 5.7 Primary Active Transporters

Figure 5.15 Mechanism of the Na +-K+-ATPase

Slide 5
ECF
[Na+] high

ADP + energy

High-affinity binding
sites for Na+ appear.
3 Na+ from ICF bind
to high-affinity sites.
ICF
[Na+] low

K-binding sites
lose their affinity
for K+ and release
2 K+ into ICF.

Pi released.

Protein changes
conformation.
2 K+ from ECF bind
to high-affinity sites.

ATPase is
phosphorylated
with Pi from ATP.
Protein changes
conformation.
Na-binding sites lose their affinity
for Na+ and release 3 Na+ into ECF.

[K+ ] low

[K+ ] high
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High-affinity
binding sites
for K+ appear.

Table 5.8 Examples of Secondary Active Transporters

Figure 5.16 Mechanism of the SGLT transporter

Na+ binds to carrier.
Intracellular fluid

Lumen of intestine
or kidney
Na+

SGLT protein

[Na ] high
+

Glu
[glucose] low
[Na+] low
[glucose] high

Na+ binding creates

a high-affinity site
for glucose.

Na+

Glu
Lumen

Na+

Gl

Glucose binding changes

carrier conformation so
that binding sites now
face the ICF.

ICF

Lumen

Na+ is released into cytosol,

where [Na+] is low. Release
changes glucose-binding
site to low affinity. Glucose
is released.

ICF

Na+
Glu

[Na+] low
[glucose] high

Lumen

ICF

Table 5.6 Rules for Diffusion of Uncharged Molecules

Factors affecting rate of diffusion

through a cell membrane:

Lipid solubility
Molecular size
Concentration gradient
Membrane surface area
Composition of lipid layer

Figure 5.10 ESSENTIALS Membrane Transporters

+Tonicity and osmolality

cells bath in ECF

+Tonicity versus Osmolarity

Osmosis:

Osmosis is the movement of water across a membrane in response to a solute concentration

gradient. = the total concentration of ALL solutes in the solution.

Osmotic pressure is the pressure that must be applied to against the osmosis.

Molarity (1M NaCl) versus osmolarity (2 OsM)

Osmolarity(osmo/L) =molarity (mole/L)X particles /moles (osmol/mol)

Isosmotic, hyperosmotic, and hyposmotic

Compare the number directly

Tonicity

The ability of an extracellular solution to make water

move into or out of a cell by osmosis is know as its
tonicity.

Tonicity depends on nonpenetrating (N) solutes only

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Tonicity versus Osmolarity

physiological terms to describe a
solution how that solution would
affect the cell volume.
Tonicity refers to what
cell does in a certain
environment. Isotonic,
hypertonic(H2O moves
out cells=shrink), and
hypotonic(H2O in=swell)

Tonicity depends on
nonpenetrating (N)
solutes only

Osmolality refers to the

concentration of two
solutions. Higher
osmolality = higher
concentration of total
solutes.

hypertonic

isotonic

hypotonic
Figure 5-xx

Table 5.2 Comparing Osmolarities

Tonicity and osmolarity generally will have the same prefix. However,
there are some solutes that will act oddly and can create a situation
where the system is hypertonic and isoosmotic. Just look at what the
cell does and relative concentration of each solution, and you can
figure it out.

Table 5.5 Intravenous Solutions

Intracellular OsM=286 mOsM: Extra Cellular Fluid (ECF) >, =, < 286 mOsM

0.9% NaCl= 0.9 gram per 100mL H2O~154mmole/L

=154X2X0.93(coefficient)=286 mOsM
5% dextrose=5 gram dextrose per 100mL =278 mmol/L
=278 mOsM

+
Electrical signals

+ Homeostasis Does Not Mean Equilibrium

semipermeable membrane

Osmotic equilibrium
Chemical disequilibrium
Electrical disequilibrium

Figure 5.1

Separation
of
Electrical
Charges
+
Figure 5-23b

Resting membrane potential is the electrical

gradient between ECF and ICF

Electrical Signals: Nernst Equation

Describes the membrane potential that

a single ion would produce if the
membrane were permeable to only that
ion (Eion in mV)

Membrane potential is influenced by

Concentration gradient of ions
Membrane selective permeability to
those ions

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Electrical Signals:
GHK (Goldman-Hodgkin-Katz) Equation
Predicts membrane potential that results from the contribution of all ions
that can cross the membrane

P: the relative permeability of membrane to the ion

Table 8.2 Ion Concentrations and Equilibrium Potentials

Potassium
Equilibrium
Potential
+

Resting

membrane potential is due mostly to potassium

Figure 5-24

+ Electrical Concerns
1.

Opposite charges attract; like charges repel each other

2.

Separating positive charges from negative charges requires energy

3.

A gradient of charges across a membrane is called an electrical

potential (charge difference)

4.

Electrical potentials affect diffusion of ions.

5.

Osmolar/tonic gradients and electric gradients are both forces placed

upon cells.

6.

Cells have many large fixed anions (proteins, fatty acids, DNA, RNA)

7.

Cells have a negative charge, compared to the outside

8.

All cells have a resting membrane potential around -70mV

Electrical Signals: Ion Movement

Resting membrane potential determined primarily by

K+ concentration gradient

Cells resting permeability to K+, Na+, and Cl

Gated channels control ion permeability

Mechanically gated: hair cells calcium channel

Chemically gated: AMPA receptor-Na channel

Voltage-gated: sodium channel, L-type Calcium channel

Threshold voltage varies from one channel type to another

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Figure 8.10a (1 of 5)

Na+
ECF

ICF
Activation
gate

30
0
mV
55
70

Inactivation
gate

At the resting membrane potential, the activation gate

closes the channel.

Figure 8.10b (2 of 5)

Na+
30
0
mV
55
70

Depolarizing stimulus arrives at the channel. Activation gate opens.

+
Only muscle cells and neurons
can be excitable!

Figure 8.13

LOW CURRENT FLOW

When a section of axon depolarizes, positive charges
move by local current flow into adjacent sections of the
cytoplasm. On the extracellular surface, current flows
toward the depolarized region.
Local current flow is a wave of
depolarization that moves
through the cell
Graded potentials lose strength as
they move through the cell due to
Current leak
Cytoplasmic resistance

Depolarized section
of axon

If strong enough, graded

potentials reach the trigger zone
in the axon hillock and initial
segment action potential

Changes
in
Membrane
Potential
+

Terminology associated with changes in membrane potential

Figure 5-26

Figure 8.12
REFRACTORY PERIODS FOLLOWING AN ACTION POTENTIAL
A single channel shown during a
phase means that the majority of
channels are in this state.

Both
Na+
channels channels
closed
open

Where more than one channel of a

particular type is shown, the
population is split between the states.

Na+ channels close and

K+ channels open

Both
channels
closed

Na+ channels reset to original position

while K+ channels remain open

Na+ and K+
channels
K+

K+

K+

Absolute refractory period

During the absolute refractory period, no
stimulus can trigger another action potential.

Relative refractory period

During the relative refractory period, only a larger-thannormal stimulus can initiate a new action potential.

High

+30

Ion permeability

0
Na+

K+

55
70
Low

High

High

Excitability

Na channel
threshold

Membrane potential (mV)

Action potential

Increasing

Zero
0

2
Time (msec)

Action Potentials Travel Long Distances

Conduction is the high-speed movement of a action potential

along an axon
All-or-none
During the absolute refractory period, no
stimulus can trigger another action potential.
AP appears only at node of Ranvier

A wave of electrical current passes down the axon.

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Figure 8.16a (1 of 2 ) Ranvier = where AP happens= myeline sheath gaps

Action potentials appear to jump from one node of Ranvier to the next. Only the nodes have voltage-gated Na + channels.
Node

Node

Node of Ranvier

Myelin sheath

Na+

Depolarization

In demyelinating diseases, conduction slows when current leaks out of the previously insulated regions between the nodes.
Degenerated
myelin sheath
Na+

Current leak
slows conduction

A&P FlixTM: Propagation of an Action Potential

+Electrical Signals: Speed of Action Potential

Speed

of action potential in neuron influenced by

Diameter of axon
Larger axons are faster
ion easier to pass through cytoplasm
Resistance of axon membrane to ion leakage out of the
cell
Myelinated axons are faster (150 m/s vs 0.5~10 m/s
unmyelinated axons)
Saltatory conduction between nodes of Ranvier
Express lane and local lane
Youtube: Action potential speed

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Integration of electrical signal

Cell-cell communication

Figure 8.9-1 ESSENTIALS The Action Potential

PNa

Membrane potential (mV)

30
10
0
10

PNa

Resting membrane potential

Depolarizing stimulus

Membrane depolarizes to threshold.

Voltage-gated Na and K
channels begin to open.

Rapid Na entry depolarizes cell.

Na channels close and slower

K channels open.

K moves from cell to extracellular

fluid.

K channels remain open and

additional K leaves cell, hyperpolarizing it.

Voltage-gated K channels close,

less K leaks out of the cell.

Cell returns to resting ion permeability

and resting membrane potential.

PK

30
50

Threshold

70
PK

90
0

Figure 8.24c ESSENTIALS Summation

No summation. Two subthreshold graded potentials will

not initiate an action potential if they are far apart in time.

Membrane potential (mV)

Stimuli
(X1 & X2)

Threshold

55

70

A1
X1

A2
X2

Time (msec)

Figure 8.24d ESSENTIALS Summation in time

Summation causing action potential. If two subthreshold

potentials arrive at the trigger zone within a short period of time,
they may sum and initiate an action potential.

Stimuli
(X1 & X2)

30

Membrane potential (mV)

This threshold is to
activate sodium
channel.

Threshold

55
A2
70

A1

X1

X2

Time (msec)

Figure 8.24a ESSENTIALS Summation in space

Slide 3

Presynaptic
axon terminal

Three excitatory neurons fire. Their

graded potentials separately are all
below threshold.

Trigger zone @ axon hilllock

Action
Graded potentials arrive at trigger
zone together and sum to create a potential
suprathreshold signal.
An action potential is generated.
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Figure 8.24b ESSENTIALS Summation

Slide 2

Inhibitory
neuron

Trigger zone

One inhibitory and two

excitatory neurons fire.
No
action
potential

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The summed potentials

are below threshold, so no
action potential is generated.

Figure 8.19a ESSENTIALS Synaptic Communication

Slide 4

An action potential depolarizes

the axon terminal.
Synaptic
vesicle with
neurotransmitter
molecules

Action potential
arrives at
axon terminal

The depolarization opens

voltage-gated Ca2+ channels,
and Ca2+ enters the cell.
Calcium entry triggers
exocytosis of synaptic vesicle
contents.

Ca2+

Docking protein

Synaptic
cleft

Receptor
Postsynaptic cell

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Voltage-gated
Ca2+ channel

Neurotransmitter diffuses across

the synaptic cleft and binds with
receptors on the postsynaptic
cell.

Table 8.4 Major Neurocrines

Figure 8.23 ESSENTIALS Fast and Slow Postsynaptic Responses

Slide 7

Presynaptic axon
terminal

Inotropic
receptors

Metabotropic
receptors
Neuromodulators

Neurotransmitters
create rapid, short-acting
fast synaptic potentials.

create slow synaptic

potentials and longterm effects.

Neurocrine

G proteincoupled
receptor

Chemically
gated ion channel

R
G
Postsynaptic
cell

Alters open
state of
ion channels

Ion channels
open

More
Na+ in

EPSP =
excitatory
depolarization

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Inactive
pathway
Activated second
messenger pathway

Ion channels
close

More K+
out or
Cl in

Less
Na+ in

IPSP =
inhibitory
hyperpolarization

Modifies existing
proteins or
regulates synthesis
of new proteins

Less K+
out

EPSP =
excitatory
depolarization

Coordinated
intracellular
response

Figure 8.19b ESSENTIALS Synaptic Communication

Neurotransmitter Termination
Neurotransmitter action terminates when the chemicals are broken down,
are taken up into cells, or diffuse away from the synapse.
Blood
vessel
Axon
terminal of
presynaptic cell

Neurotransmitters can be returned

to axon terminals for reuse or
transported into glial cells.

Synaptic
vesicle

Enzymes inactivate
neurotransmitters.

Glial
cell

Neurotransmitters can diffuse

out of the synaptic cleft.

Enzyme
Postsynaptic cell

Cell-to-Cell: Neurons Communicate at Synapses

Electrical synapses pass electrical signals through gap junctions

Chemical synapses use neurotransmitters that cross synaptic

clefts

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Figure 8.26a (1 of 9)

Slide 3

Inhibitory neuron

No neurotransmitter
release
Target cell

Presynaptic
axon terminal

No response

Excitatory
neuron
Response

Action potential
Neurotransmitter
released

Response

An excitatory neuron
fires.

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An action potential
is generated.

An inhibitory neuron fires, blocking

neurotransmitter release at one
synapse.

Figure 8.26b (5 of 9)

In postsynaptic inhibition, all targets of the postsynaptic neuron are inhibited equally.

No response

Inhibitory neuron modifies the signal.

IPSP

EPSP

No response

Excitatory
neuron

No response

One excitatory and one

inhibitory presynaptic
neuron fire.

Modified signal in
postsynaptic neuron
below threshold.

No action potential
initiated at trigger zone.

No response in
any target cell.

Integration: Long-Term Potentiation and Depression

Activity at a synapse induces sustained changes in quality or quantity of

connections

Glutamate is key element in potentiation

May be related to learning, memory, depression, and mental illness

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+ Electrical Signals:
Graded

start @trigger Zone

potential enters trigger zone

Voltage-gated

Na+ channels open, and Na+ enters axon

Positive

charge spreads along adjacent sections of axon by local

current flow

Local

current flow causes new section of the membrane to

depolarize

K+

channels open and Na channels close

The refractory period (inactive Na channel) prevents backward conduction

K+

current repolarizes the membrane

Na,

K and other ion gradients are restored.

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+Cell-to-Cell neurotransmitters

Seven classes by
structure

Acetylcholine

Amines

Amino acids

Peptides

Peptide P
Substance P

Opiod

Purines

Gases

Lipids

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Inotropic receptors
Receptor-channels
Mediate rapid responses
Alter ion flow across
membranes

Metabotropic receptors
G proteinmediated
receptors
Mediate slower responses
Some open or close ion
channels

+Contact between neurons and glia cells

Chemical synapse and electrical synapse

Summary

Cells of the nervous system

Neurons; glial cells

Neuron basic anatomy

Electrical signals in neurons

Na channel, K channel

AP

Refractory period

Integration of neural information transfer

Summation in time and in space

Cell-to-cell communication in the nervous system

Neurotransmitters:

receptors

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