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T2 Cellular Physiology of Nerve & Muscle Part 1

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Topic 2: Cellular
Physiology of
Nerve and Muscle
(Part 1)
Required Readings:
• Plasma Membrane: Chapter 3: p. 63-81
• Neurons: Chapter 11: p.394 (neurons) –
397 (myelination); p. 400 – 420
• Muscle: Chapter 9: p. 279 - 314
Université d’Ottawa | University of Ottawa
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Objectives Part I
Membrane Transport
2.1.1. Describe the structure of the plasma membrane
2.1.2. Describe and differentiate among the various types of transport across the
plasma membrane
2.1.3. Describe osmosis and explain its role in fluid homeostasis
Neurons
2.2.1 Identify the different regions of the neuron and associate each region with the
functions of reception, propagation and transmission of nerve impulses
2.2.2.Explain the phenomena (diffusion of ions, types of ion channels) that are
responsible for the electrical activity of neurons (resting membrane potential,
action potential)
2.2.3 Describe the factors that influence propagation of the action potential along an
axon
2.2.4 Explain the mechanisms of synaptic transmission (synapse, post-synaptic
potentials, synaptic integration)
PLASMA MEMBRANE
• Also known as the “cell membrane”
• acts as an active barrier separating intracellular fluid (ICF) from extracellular fluid
(ECF)
• selectively permeable /plays role in cellular activity by controlling what enters and
what leaves cell
• allows the cell to respond to changes in the extracellular fluid
• communication: site of cell-to-cell interaction and recognition
PLASMA MEMBRANE
Basic structure according to
fluid mosaic model:
• phospholipid bilayer
• Membrane proteins
• Surface sugars form
glycocalyx
• Membrane structures
help to hold cells
together through cell
junctions
PLASMA MEMBRANE
• Lipid bilayer
– 75% phospholipids, which consist of two parts:
 Phosphate heads: are polar (charged), so are hydrophilic (water-loving)
 Fatty acid tails: are nonpolar (no charge), so are hydrophobic (water-hating)
– 5% glycolipids
 Lipids with sugar groups on outer membrane surface
– 20% cholesterol
 Increases membrane stability
PLASMA MEMBRANE
Membrane Proteins
• Make up about half the mass of
plasma membrane
• Allow cell communication with
environment
• Most have specialized membrane
functions
• Some float freely, and some are
tethered to intracellular structures
PLASMA MEMBRANE
Two types
Integral proteins
• Firmly inserted into membrane
• Most are transmembrane proteins (span membrane)
• Have both hydrophobic and hydrophilic regions
 Function as transport proteins (channels and carriers), enzymes, or
receptors
Peripheral Proteins
• Loosely attached to integral proteins
• Include filaments on intracellular surface
used for plasma membrane support
Function as:
o Enzymes
o Motor proteins for shape change
during cell division and muscle
contraction
o Cell-to-cell connections
Functions of Plasma Membrane Proteins
(a)Transport
 A protein (left) that spans the membrane may provide a hydrophilic
channel across the membrane that is selective for a particular solute.
 Some transport proteins (right) hydrolyze ATP as an energy source to
actively pump substances across the membrane.
(b) Receptors for signal transduction
 A membrane protein exposed to the outside of the cell may have a
binding site that fits the shape of a specific chemical messenger,
such as a hormone.
 When bound, the chemical messenger may cause a change in
shape in the protein that initiates a chain of chemical reactions in the
cell.
(c) Enzymatic activity
 A membrane protein may be an enzyme with its active site exposed
to substances in the adjacent solution.
 A team of several enzymes in a membrane may catalyze sequential
steps of a metabolic pathway as indicated (left to right) here.
Functions of Plasma Membrane Proteins
(d) Cell-cell recognition
 Some glycoproteins (proteins bonded to short chains of sugars which
help to make up the glycocalyx) serve as identification tags that are
specifically recognized by other cells.
(e) Attachment to the cytoskeleton and
extracellular matrix (ECM)
 Elements of the cytoskeleton (cell’s internal framework) and the
extracellular matrix (fibers and other substances outside the cell) may
anchor to membrane proteins.
 Helps maintain cell shape, fixes the location of certain membrane
proteins, and plays a role in cell movement.
(f) Cell-to-cell joining
 Membrane proteins of adjacent cells may be hooked together in
various kinds of intercellular junctions.
 Some membrane proteins (cell adhesion molecules or CAMs) of this
group provide temporary binding sites that guide cell migration and
other cell-to-cell interactions.
PLASMA MEMBRANE
Membrane Carbohydrates and Glycocalyx
• Consists of sugars
(carbohydrates) sticking out of
cell surface
– Some sugars are attached
to lipids (glycolipids) and
some to proteins
(glycoproteins)
• Every cell type has different
patterns of this “sugar coating”
– Functions as specific
biological markers for cellto-cell recognition
– Allows immune system to
recognize “self” vs. “nonself”
Cell Junctions
MEMBRANE TRANSPORT
• Substances must constantly move across the plasma membrane
– Some molecules pass through easily; some do not
• Plasma membrane is selectively permeable allowing only certain molecules to
cross
• Two essential ways substances cross plasma membrane:
– Passive transport: no energy is required
– Active transport: energy (ATP) is required
Passive Transport
Three types of passive transport
 Simple Diffusion
 Facilitated diffusion
 Osmosis
• All types involve diffusion – natural movement of molecules from areas of
high concentration to areas of low concentration
• Also referred to as moving down a concentration gradient
GRADIENTS
Concentration gradient
Electrical gradient
Passive Transport
Diffusion
• Movement down a concentration gradient. What is a gradient?
• Molecules in higher concentration areas collide more resulting in molecules being
scattered to lower concentration areas
Speed of diffusion influenced by 3 factors:
– Concentration: the steeper the gradient, the faster diffusion occurs
– Molecular Size: smaller molecules diffuse faster
– Temperature: higher temps increase kinetic energy which results in faster diffusion
Equilibrium is reached when there is no net movement of molecules in one direction only
What determines whether a substance can cross the plasma membrane?
 Lipid-soluble and nonpolar substances
 Size: Very small molecules that can pass through membrane or membrane channels
Passive Transport
Simple Diffusion
• Nonpolar, lipid-soluble (hydrophobic) substances diffuse directly
through phospholipid bilayer e.g., O2, CO2, steroid hormones,
fatty acids
• Small amounts of very small polar substances, such as water, can
even pass
Facilitated Diffusion

Larger or non-lipid soluble or polar molecules can cross
membrane but only with assistance of carrier molecules
Referred to as facilitated diffusion
 Certain hydrophilic molecules (e.g., glucose, amino acids, and ions) are transported
passively down their concentration gradient by:
• Carrier-mediated facilitated diffusion
– Substances bind to protein carriers
• Channel-mediated facilitated diffusion
– Substances move through water-filled channels
Passive Transport
Facilitated Diffusion
A.Carrier-Mediated
• lipid-insoluble molecules too large to pass
through membrane pores/channels
• Carriers are transmembrane integral proteins
Features of carrier mediated diffusion:
1. specific
2. not ATP-requiring
3. limited by carrier saturation. What is the
transport maximum?
4. movement down concentration gradient
5. can be inhibited by certain substances
What is the most well-known substance that is
transported by carrier-mediated facilitated diffusion?
Passive Transport
Facilitated Diffusion
B. Channel-Mediated
• Channels with aqueous-filled cores are formed by
transmembrane proteins
• Channels transport molecules such as ions or water
(osmosis) down their concentration gradient
• selective due to pore size, charge of a.a. that
line channels
• Water channels are called aquaporins
Two types:
• Leakage channels: are always open
• Gated channels: opening is controlled by chemical
or electrical signals
Note:
• Movement always down concentration gradient
• Can be inhibited, can show saturation & are usually
specific
Osmosis
– Special name for movement of solvent
(not molecules), such as water, across a
selectively permeable membrane
– Water diffuses across plasma
membranes
• through lipid bilayer (even though
water is polar, it is so small that
some molecules can sneak past
nonpolar phospholipid tails)
• through specific water channels
called aquaporins (AQPs)
– Flow occurs when water (or other
solvent) concentration is different on the
two sides of a membrane
Osmosis
Osmolarity: measures the concentration of the total number of solute particles
in solvent
Does a solution of 1 M NaCl have the same
osmolarity as a solution on 1 M MgCl2?
 solutions of different osmolarities
separated by a membrane permeable to
all molecules:
• diffusion of solutes & osmosis of H2O
occur across membrane 
equilibrium of solutes & H2O is
reached
 Solutions of different osmolarities
separated by a membrane permeable only
H2O
• only osmosis (not diffusion) will
occur until equilibrium is reached
Osmosis
Movement of water involves pressures:
– Hydrostatic pressure: outward pressure
exerted on cell side of membrane caused
by increases in volume of cell due to
osmosis
 Also referred to as “back pressure”
–
Osmotic pressure: inward pressure due to
tendency of water to be “pulled” into a cell
with higher osmolarities
 The more solutes inside a cell the
bigger the pull on water to enter,
resulting in higher osmotic pressures
inside the cell
http://upload.wikimedia.org/wikipedia/commons/
0/03/Illu_capillary_microcirculation.jpg
Osmosis
Tonicity
 Ability of a solution to change the shape or tone of
cells by altering the cells’ internal water volume
• Isotonic solution has same osmolarity as inside the cell, so volume remains unchanged
• Hypertonic solution has higher osmolarity than inside cell, so water flows out of cell, resulting
in cell shrinking
– Shrinking is referred to as crenation
• Hypotonic solution has lower osmolarity than inside cell, so water flows into cell, resulting in
cell swelling
– Can lead to cell bursting, referred to as lysing
The effect of solutions of
varying tonicities on living
red blood cells
Active Transport
Two major active membrane transport
processes
• Primary & Secondary
 Like facilitated diffusion both
require carrier proteins (solute
pumps): combines specifically &
reversibly with substance
 unlike facilitated diffusion,
solute pumps move
substances (amino acids, Na+,
K+, Ca+) AGAINST
CONCENTRATION
GRADIENTS
https://i.ytimg.com/vi/WgmJ8NKLgAg/maxresdefault.jpg
Active Transport
1. Primary Active Transport
• Requires energy directly from ATP hydrolysis
– Energy from hydrolysis of ATP causes change in shape of transport protein
– Shape change causes solutes (ions) bound to protein to be pumped across
membrane
+
+
– Example of pumps: calcium, hydrogen (proton), 𝑁𝑎 −𝐾 pumps
Most studied is the Na+-K+ pump
– An enzyme, called Na+-K+ ATPase, that pumps Na+ out
of cell and K+ back into cell
– Located in all plasma membranes, but especially active
in excitable cells (nerves and muscles)
•
•
[K+] 10-20X higher inside cell than out; [Na+] higher
outside cell
gradients essential to maintain normal cell
function/responsiveness/volume
Maintenance of this gradient challenged by:
i. slow leakage of K+ and Na+ along conc. gradients
ii. stimulation of muscle & nerve cells
Na+/K+ ATPase functions continuously to maintain Na+ & K+ gradients
Active Transport
Primary active transport
• the process in
which solutes are
moved across cell
membranes
against
electrochemical
gradients using
energy supplied
directly by ATP.
Resting Membrane Potential
Resting membrane potential (RMP)
– Electrical potential energy produced by separation of oppositely charged
particles across plasma membrane in all cells
• Difference in electrical charge between two points is referred to as voltage
• Cells that have a charge are said to be polarized
– Voltage occurs only at membrane surface rest of cell is neutral
+
𝑲 is Key Player in RMP
• RMP maintained by the
+
+
𝑁𝑎 −𝐾 pump
• Neuron & muscle cells
“upset” this steady state
RMP by intentionally
+
+
opening gated 𝑁𝑎 and 𝐾
channels
http://site.motifolio.com/images/Passive-and-active-fluxes-maintainthe-resting-membrane-potential-5111223.png
Active Transport
2. Secondary Active Transport
 Also called cotransport
 Required energy is obtained indirectly from ionic gradients created by
primary active transport
Many active transport systems are coupled
systems
 Antiporters transport one substance into
cell while transporting a different
substance out of cell e.g. Na+ -K+ ATPase
 Symporters transport two different
substances in the same direction e.g. Na+
& amino acids or glucose, Na+, K+, Clcotransporter
https://www.apsubiology.org/anatomy/2010/2010_Exa
m_Reviews/Exam_1_Review/uni-sym-antiport.jpg
Active Transport
Secondary Active Transport
+
• Low 𝑁𝑎 concentration that is
+
maintained inside cell by 𝑁𝑎
+
− 𝐾 pump strengthens
sodium’s drive to want to enter
cell
+
• 𝑁𝑎 can drag other molecules
with it as it flows into cell
through carrier proteins (usually
symporters) in membrane
 Some sugars, amino acids, and
ions are usually transported into
cells via secondary active
transport
Vesicular Transport
• Transport of large particles, macromolecules, and fluids
across membrane in membranous sacs called vesicles
• Requires energy supplied by ATP
Vesicular transport processes include:
– Endocytosis: transport into cell
• 3 different types of endocytosis: phagocytosis,
pinocytosis, receptor-mediated endocytosis
– Exocytosis: transport out of cell
– Transcytosis: transport into, across, and then out of cell
– Vesicular trafficking: transport from one area or
organelle in cell to another
Vesicular Transport
Endocytosis
– Involves formation of protein-coated
vesicles
– Usually involve receptors; therefore can
be a very selective process
 Substance being pulled in
must be able to bind to its
unique receptor
– Some pathogens are capable of
hijacking receptor for transport into cell
– Once vesicle is pulled inside cell, it
may:
 Fuse with lysosome or
 Undergo transcytosis
Endocytosis mediated by protein coated pits
Vesicular Transport
Endocytosis
Phagocytosis
Pinocytosis
•
•
The cell engulfs a
large particle by
forming a projecting
pseudopod (“false
foot”) around it and
enclosing it within a
membranous sac
called a phagosome
The cell “gulps” a drop
of extracellular fluid
containing solutes into
tiny vesicles. No
receptors are used, so
the process is
nonspecific.
Receptor-mediated
endocytosis
•
Extracellular substances
bind to specific receptor
proteins, enabling the cell to
ingest and concentrate
specific substances in
protein-coated vesicles.
Substances may be
released inside the cell or
digested in a lysosome.
Vesicular Transport
Exocytosis: process where material is ejected from cell
Neurons
Jump to Chapter 11 here
o structural units of nervous system
o Large, highly specialized cells that conduct impulses
3 functional regions:
(plasma membrane very
important in all regions!)
1. Receptive region
2. Conducting region
3. Secretory region
Figure 11.5a Structure of a motor neuron.
Neurons
Special characteristics
 Extreme longevity (lasts a person’s lifetime)
 amitotic, with few exceptions
 High metabolic rate requires continuous supply of oxygen and glucose
 All have cell body and one or more processes
Neuron Cell Body (Perikaryon or Soma)
• large, spherical nucleus + granular cytoplasm
 biosynthetic centre: synthesizes proteins,
membranes, chemicals
 extensive rough ER + ribosome clusters
(Nissl bodies); also elaborate Golgi & lots of
mitochondria. Why??
Most neuronal cell bodies are located in CNS
• Nuclei: clusters of neuronal cell bodies in CNS
• Ganglia: clusters of neuronal cell bodies in PNS
Neurons
Neuronal Processes: arm like processes that extend from cell body
Dendrites: receptive (input) region; Convey
incoming messages toward cell body
• short, tapering, branched extensions;
usually hundreds/cell body
• enormous SA for reception from other
neurons
• conduct impulses toward cell body
• short distance, graded potentials
Neurons
Axon: conducting region
• arises from axon hillock; variable length (can be
> 1m)
• usu. 1 axon/neuron; branches at end into axonal
terminals or axon telodendria (~10,000)
• rate of conduction increases with axon diameter
• Neurotransmitters convey information from one
axon to the next
• Axon has same organelles as cell body, but no
Nissl bodies; axons quickly degenerate if cut
Tracts: Bundles of neuronal axons in CNS
Nerves: Bundles of neuronal axons in PNS
Elaborate cytoskeleton in axon to
move material to & from:
• Anterograde: (eg: mitos,
cytoskeleton, membrane parts,
NTs)
• Retrograde: (eg: organelles to be
degraded/recycled)
Neurons
Axon: conducting region
Myelin sheath
 Composed of myelin, a whitish, protein-lipid substance
– Function of myelin
• Protect and electrically insulate axon
• Increase speed of nerve impulse transmission
Figure 11.6a PNS nerve fiber myelination.
A Clinical Note
Multiple Sclerosis
• persistent inflammatory response in which
myelin sheaths gradually destroyed
(autoimmune? persistent virus?)
 Turns myelin into hardened lesions
called scleroses
 Impulse conduction slows and
eventually ceases
• cycles of remission and relapse: flare-ups
and then some healing and myelin
regeneration; axons develop more Na+
channels in demyelinated areas
Symptoms:
• blindness (optic nerve), muscle weakness,
clumsiness, urinary incontinence
• ultimately myelin destruction is permanent
and axons “drop out” or degenerate
https://www.mayoclinic.org/-/media/kcms/gbs/patientconsumer/images/2015/03/25/08/29/mcdc7_multiple_s
clerosis_myelin_damage_nervous_system-8col.jpg
Basic Principles of Electricity
• Opposite charges are attracted to each other
• Energy is required to keep
opposite charges separated
across a membrane
• When opposite charges are
separated, the system has
potential energy
• Energy is liberated when the
charges move toward one
another
http://site.motifolio.com/images/Passive-and-active-fluxes-maintainthe-resting-membrane-potential-5111223.png
Basic Principles of Electricity
Definitions
 Voltage: a measure of potential energy generated
by separation (PM) of oppositely charged ions
• Measured between two points in volts (V) or millivolts
(mV)
• Called potential difference or potential
• Charge difference across plasma membrane results
in potential
Greater charge difference between points = higher
voltage
 Current: flow of electrical charge (ions) between two points
• Flow is dependent on voltage & resistance; can be used to do work
 Resistance: hindrance to charge flow
• Insulator: substance with high electrical resistance
• Conductor: substance with low electrical resistance
Basic Principles of Electricity
Role of membrane ion channels
• Large proteins serve as selective membrane ion channels
• K+ ion channel allows only K+ to pass through
Two main types of ion channels
• Leakage (nongated) channels: always open
• Gated channels, in which part of the protein changes shape to
open/close the channel. 3 main gated channels:
1. Chemically gated Channels : open only with binding of a specific chemical
(neurotransmitter/hormone)
2. Voltage−gated: open and close in response to changes in membrane
potential
3.
Mechanically gated: Open and close in response to physical deformation of
receptors, as in sensory receptors
Operation of Gated Channels
channels ion-specific: channels open >> ions move
in response to electrochemical gradients
Generating the Resting Membrane Potentials
• all cells are polarized; RMP cell-type-dependent
• neurons have a resting membrane potential
Membrane potential generated by:
• Differences in ionic composition of Intracellular fluid and Extracellular Fluid
– ECF has > concentration of
+
𝑁𝑎 than ICF
• Balanced chiefly by
chloride ions (𝐶𝑙)
– ICF has higher
concentration of K+ than
ECF
• Balanced by negatively
charged proteins
– K+ plays the most important
role in membrane potential
Generating the Resting Membrane Potentials
Differences in plasma membrane permeability
• Impermeable to large anionic proteins
• Slightly permeable to Na+ (through leakage channels)
• Sodium diffuses into cell down concentration gradient
• 25 times more permeable to K+ than sodium (more leakage
channels)
• Potassium diffuses out of cell down concentration gradient
• Quite permeable to Cl–
• Sodium-potassium pump (Na+/K+ ATPase) stabilizes resting
membrane potential
• Maintains concentration gradients for Na+ and K+
• Three Na+ are pumped out of cell while two K+ are pumped back in
Generating the Resting Membrane Potentials
Neurons are highly excitable
What do we mean when we say that neurons are excitable cells??
A&P Flix™: Resting Membrane Potential
Check your understanding
Check all descriptions that apply to a resting neuron:
1.
Its inside is negative relative to its outside.
2.
Its outside is negative relative to its inside.
3.
The cytoplasm contains more Na+ and less K+ than does the ECF.
4.
The cytoplasm contains more K+ and less Na+ than does the ECF.
5.
A charge separation exists at the plasma membrane.
6.
The electrochemical gradient for the movement of Na+ across the
membrane is greater than that for K+.
7.
The electrochemical gradient for the movement of K+ across the
membrane is greater than that for Na+.
8.
The membrane is more permeable (leaky) to Na+ than to K+.
9.
The membrane is more permeable (leaky) to K+ than to Na+.
Changing the Resting Membrane Potential
When does membrane potential change?
Depolarization: decrease in membrane
potential (moves toward zero & above)
 Inside of membrane becomes less negative
than RMP
 Increases probability of producing impulse
Hyperpolarization: increase in membrane
potential (away from 0)
 Inside of membrane becomes more negative
than RMP
 Decreases probability of producing impulse
Changes produce two types of signals
• Graded potentials: ………………
• Action potentials: ………………..
• Changes used as signals to receive, integrate and send information
Graded Potentials
Short-lived, localized changes in membrane potential
• Triggered by stimulus that opens gated ion channels
• Results in depolarization or sometimes hyperpolarization
• The stronger the stimulus, the more voltage changes and the farther the current flows
• decremental movement of ions on either side of membrane propagates signal for short
distance
Named according to location and function
• Receptor potential (generator potential):
 graded potentials in receptors of sensory
neurons
• Postsynaptic potential: neuron graded potential
Action Potentials
Brief reversal of membrane potential with a change in
voltage of ~100 mV (from -70 to +30 mV) in a patch of
membrane depolarized by local currents
• principal way neurons send signals
• means of long-distance neural communication
• do not decay in amplitude with distance traveled as
graded potentials do
• occur only in cells with excitable membranes
(neurons & muscle cells)
• in neurons
• only axons can generate action potentials
• also referred to as a nerve impulse
voltage-gated channels on axons open
& close in response to local currents
(graded potentials) 
https://www.moleculardevices.com/sites/default/f
iles/images/page/what-is-action-potential.jpg
Generation of an Action Potential
Four main steps
1. Resting state: All gated 𝑵𝒂+ and K+ channels are closed
 normal leakage
 Each Na+ channel has two voltagesensitive gates
• Activation gates
• Inactivation gates
 Each K+ channel has one voltagesensitive gate
• Closed at rest
• Opens slowly with depolarization
 local depolarization: voltage-gated Na+
channels open (fast activation gates)
Generation of an Action Potential
2. Depolarization: Na+ channels open
 Depolarizing local currents open voltagegated Na+ channels, and Na+ rushes into
cell
– Na+ activation & inactivation gates
open
 Na+ influx causes more depolarization,
which opens more Na+ channels
 As a result, ICF becomes less –ve
 At threshold (–55 to –50 mV), positive
feedback causes opening of all
Na+ channels
 Results in large action potential spike
 Membrane polarity jumps to +30 mV
Both Na+ gates must be open for entry;
closure of either gate stops Na+ entry
What does threshold (-55 to -50 mV) mean?
Generation of an Action Potential
3. Repolarization: Na+ channels are inactivating, & K+ channels open
 Na+ channel inactivation gates
close
• AP spike stops rising
 Voltage-gated K+ channels open
• K+ exits cell down its
electrochemical gradient
 Repolarization: membrane
returns to resting membrane
potential
Generation of an Action Potential
4. Hyperpolarization: some K+ channels remain open, & Na+ channels
reset
 Some K+ channels remain open,
allowing excessive K+ efflux
 Inside of membrane becomes more
negative than in resting state
 This causes hyperpolarization of the
membrane (slight dip below resting
voltage)
 Na+ channels also begin to reset
Propagation of an Action Potential
 AP must traverse length of the axon to signal next neuron
Propagation rather than conduction of an AP
• Na+ influx through voltage gates in one membrane area cause local currents that cause
opening of Na+ voltage gates in adjacent membrane areas  depolarization of that area, which
in turn causes depolarization in next area
 APs are self propagating and unidirectional
Since Na+ channels closer to the AP origin are still inactivated, no new AP is
generated there  AP occurs only in a forward direction
Refractory Periods
time in which neuron cannot trigger another AP
•
Voltage-gated Na+ channels are open, so neuron cannot respond to another stimulus
Two types
Absolute refractory period
•
Time from opening of Na+ channels until
resetting of the channels
•
Ensures that each AP is an all-or-none event /
enforces one-way transmission of nerve
impulses
Relative refractory period
Follows absolute refractory period
•
•
•
•
Figure 11.13 Absolute and relative refractory periods in an AP.
Most Na+ channels have returned to their resting state
Some K+ channels still open
Repolarization is occurring
Threshold for AP generation is elevated
• Only exceptionally strong stimulus could stimulate an AP
Coding for Stimulus Intensity
• All action potentials are alike
and are independent of
stimulus intensity
• CNS tells difference between a
weak stimulus and a strong
one by frequency of impulses
• Frequency is number of
impulses (APs) received
per second
• Higher frequencies mean
stronger stimulus
Threshold and All-or-None Phenomenon
Conduction Velocity
What two factors determine conduction velocity?
 Two types of conduction depending on presence
or absence of myelin
– Continuous conduction
Conduction Velocity
–
•
•
•
Saltatory conduction
occurs only in myelinated axons & is about 30X faster
Na+ channels located at gaps
APs generated only at gaps
THE SYNAPSE
Neurons are functionally connected by synapses: junctions that mediate
information transfer
 From one neuron to another neuron
• Presynaptic vs postsynaptic neuron
• most neurons are both
 Or from one neuron to an effector cell
THE SYNAPSE
2 types of synapses: chemical and electrical
CHEMICAL SYNAPSES
•
•
Most common type
specialized for the release and binding of
neurotransmitters
“Neurotransmitters . . .function to open or close
ion channels that influence membrane
permeability and, consequently, membrane
potential.” (Marieb)
Typically composed of two parts:
– Axon terminal of presynaptic neuron: contains synaptic vesicles filled with
neurotransmitter
– Receptor region on postsynaptic neuron’s membrane: receives neurotransmitter
 Usually on dendrite or cell body
Separated by synaptic cleft (fluid-filled space of 30-50 nm)
INFORMATION TRANSFER ACROSS CHEMICAL SYNAPSES
Six steps are involved:
1. AP arrives at axon terminal of
presynaptic neuron
2. Voltage-gated Ca2+ channels open,
Ca2+ enters axon terminal
• Ca2+ flows down electrochemical
gradient from ECF to inside of axon
terminal
3. Ca2+ entry cause neurotransmitter
release
4. Neurotransmitter diffuses across
synaptic cleft and binds to postsynaptic
receptors
5. Binding of neurotransmitter opens ion
channels, creating graded potentials
INFORMATION TRANSFER ACROSS CHEMICAL SYNAPSES
6. Neurotransmitter effects are
terminated
• As long as neurotransmitter is
binding to receptor, graded
potentials will continue, so process
needs to be regulated
• Within a few milliseconds,
neurotransmitter effect is
terminated in one of three ways
• Reuptake by astrocytes or axon
terminal
• Degradation by enzymes
• Diffusion away from synaptic
cleft
Synaptic Delay
• Time needed for neurotransmitter to be released, diffuse
across synapse, and bind to receptors
• Can take anywhere from 0.3 to 5.0 ms
• Synaptic delay is rate-limiting step of neural transmission
• Transmission of AP down axon can be very quick, but
synapse slows transmission to postsynaptic neuron
down significantly
• Not noticeable, because these are still very fast
THE SYNAPSE
ELECTRICAL SYNAPSES
• Less common than chemical synapses
• Neurons are electrically coupled
• Joined by gap junctions that connect cytoplasm of adjacent neurons
• Communication is very rapid and may be unidirectional or
bidirectional
• Found in some brain regions responsible for eye movements or
hippocampus in areas involved in emotions and memory
• Most abundant in embryonic nervous tissue
Postsynaptic Potentials
• Neurotransmitter receptors cause graded potentials that vary in strength
based on:
• Amount of neurotransmitter released
• Time neurotransmitter stays in cleft
• Depending on effect of chemical synapse, there are two types of
postsynaptic potentials
• EPSP: excitatory postsynaptic potentials
• IPSP: inhibitory postsynaptic potentials
Excitatory Synapses and EPSPs
• Neurotransmitter binding opens
chemically gated channels
• Allows simultaneous flow of Na+
and K+ in opposite directions
• Na+ influx greater than K+ efflux,
resulting in local net graded potential
depolarization called excitatory
postsynaptic potential (EPSP)
• EPSPs trigger AP if EPSP is of
threshold strength
• Can spread to axon hillock and
trigger opening of voltage-gated
channels, causing AP to be
generated
what is generated is NOT an AP; only axonal membranes can generate APs!!;
get local, graded depolarizations called EPSPs; if strong enough to reach axon
hillock, then get AP
Inhibitory Synapses and IPSPs
• Neurotransmitter binding to receptor
opens chemically gated channels that
allow entrance/exit of ions that cause
hyperpolarization
• Makes postsynaptic membrane more
permeable to K+ or Cl–
• If K+ channels open, it moves out of
cell
• If Cl– channels open, it moves into cell
• Reduces postsynaptic neuron’s ability
to produce an action potential
• Moves neuron farther away from
threshold (makes it more
negative)
Integration and Modification of Synaptic Events
Summation by the postsynaptic neuron
• A single EPSP cannot induce an AP, but EPSPs can summate (add
together) to influence postsynaptic neuron
• IPSPs can also summate
• Most neurons receive both excitatory and inhibitory inputs from thousands
of other neurons
• Only if EPSPs predominate and bring to threshold will an AP be generated
Two types of summations
1. Temporal
2. Spatial
Postsynaptic Potentials and Their Summation
Temporal summation
• One or more presynaptic neurons transmit impulses in rapid-fire order
• First impulse produces EPSP, and before it can dissipate another EPSP is
triggered, adding on top of first impulse
Postsynaptic Potentials and Their Summation
Spatial summation
• Postsynaptic neuron is stimulated by large number of terminals simultaneously
• Many receptors are activated, each producing EPSPs, which can then add
together
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