Cell Physiology
Lecture 1 recording 1: Introduction to Cell Physiology
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Cell Physiology:
o Cell → functional unit of a living organism
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Basic Components of the Cell:
o Cells have different structures and different functions
o All cells contain: a plasma (cell) membrane which surrounds the cell surface, cell
organelles which compartmentalize the cell and perform specific functions, and the
interior of the cell which consists of the nucleus and the cytoplasm.
 Cell organelles: membrane-bound or non-membrane bound
 Cytoplasm: the region outside the nucleus and is composed of cytosol, a gel-like
fluid, in which the cell organelles are suspended
 The nucleus is the largest organelle in the cell
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Plasma (Cell) Membrane Functions:
o Functions of the plasma (cell) membrane:
1. Physical barrier between the intracellular (ICF) and extracellular (ECF) fluids
 Keeps organelles and proteins inside cell
 Maintains difference in ion composition between ICF and ECF
 Maintains homeostasis – things may change outside the cell but inside
remain constant
2. Cell-to-cell communication
 Contains receptors which bind signaling molecules
3. Structural support
 Contains connections composed of proteins which anchor cells to each
other or to extracellular materials
4. Transport
 Plasma membrane is selectively permeable- some substances may
simply move across the plasma membrane but most require specific
transport proteins (transporters, carriers, channels etc.) to cross. It is
therefore selectively permeable, allowing certain molecules to move
across but not others.
Lecture 1 recording 2: Composition of Biological Membranes
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Biological Membranes:
o The cell/plasma membrane and the intracellular membranes surrounding organelles are
composed of a double layer of lipid molecules with embedded proteins
 The predominant lipid is the phospholipid and biological membranes are called
phospholipid bilayers
 Phospholipid bilayer – 2 layers of phospholipids with embedded
proteins
 Biological membranes have different ratios of lipids and proteins
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Lipids:
o Biological membrane lipids (cell/plasma membrane and membranes surrounding
organelles) are amphipathic
 Amphipathic molecule – contains polar and nonpolar regions
 Amphipathic lipids found in biological membranes include
phospholipids, cholesterol, glycolipids
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Structure of a Phospholipid:
o Polar head group: phosphate attached to glycerol, a nitrogen-containing chemical
group, and glycerol backbone
 Polar head group is hydrophilic (water-loving or dissolves in water)
o Nonpolar tail: 2 fatty acid chains composed of carbon and hydrogen atoms
 Fatty acid chains may be: saturated (no double bonds) or unsaturated
(containing 1 or more double bonds)
 Nonpolar tail is hydrophobic (water-fearing or does not dissolve in water)
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Structure of a Phospholipid Bilayer:
o Phospholipids spontaneously form bilayer when put in water.
 Polar heads face aqueous environment, either the ECF or ICF
 Nonpolar tails form hydrophobic core
 Bilayer is the structure of the plasma membrane and the organelle membranes
Steroids:
o Cholesterol:
 Steroid lipid
 Amphipathic
 Nonpolar groups: carbon-hydrogen rings and a carbon-hydrogen
chemical group attached to one of the rings
 Polar group: hydroxyl group
 Found in the cell/plasma membrane
 Function: maintains proper membrane fluidity
 Very important part of plasma membrane: there is almost one molecule
of cholesterol for each molecule of phospholipid in the cell/plasma
membrane (organelle membranes contain very little cholesterol)
Glycolipids:
o Lipids with CHO (carbohydrate) attached
o Glycolipids are found in the outer leaflet of the plasma membrane
o Amphipathic due to presence of sugar
o Form the glycocalyx
 Glycocalyx: A layer of carbohydrates linked to lipids or membrane proteins
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Membrane Proteins:
o 2 types: integral (intrinsic) or peripheral (extrinsic)
o Intrinsic:
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 Amphipathic – inserted into phospholipid bilayer of plasma/cell membrane and
partially span membrane or are transmembrane proteins (completely cross
phospholipid bilayer of membrane)
 Comprise the majority (70%) of all proteins
 Examples: transporters or channels
Peripheral:
 NOT amphipathic
 Attached at the outer or inner surface of the membrane (do not penetrate into
the phospholipid bilayer)
Carbohydrates may be attached to proteins facing the extracellular surface of the
plasma membrane and these are called glycoproteins. Form the glycocalyx along with
glycolipids.
Proteins are distributed unequally between the two halves of the plasma membrane
and this is related to the function of the protein.
 Ie. A receptor in the membrane has binding sites facing the ECF so signally
molecules may arrive at the cell and bind to their receptors. These binding sites
do not face inside the cell
Lecture 1 recording 3: Cell Junctions
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Cell Junctions:
o Specialized connections that stabilize interactions and promote communication
between cells
Desmosomes:
o Adhering junctions that anchor cells together in tissues subject to considerable
stretching or mechanical stress
 Ie. Heart muscle
o Maintain structural integrity of tissue
o Made of proteins called: plaques, cadherins, intermediate filaments
 Plagues: on cytoplasmic surface of cell; anchor cadherins
 Cadherins: link cells together
 Intermediate filaments: anchor cytoplasmic surface of desmosome to
components inside cell to provide structural support
Tight junctions:
o Found in epithelial tissue specialized for molecular transport
 Epithelial tissue - composed of cells laid together in sheets with the cells tightly
connected to one another. Epithelial cells have two surfaces that differ in both
structure and function.
o Made of proteins called occludins which:
1. Form nearly impermeable junctions
2. Link adjacent cells together
3. Limit the movement of molecules between cells, forcing molecules to pass
through the cell, or cross the plasma membrane (molecules can only cross the
plasma membrane if they can diffuse through the lipid bilayer or have specific
proteins in the membrane)
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4. Limit the movement of integral membrane proteins and lipids
Gap junctions:
o Transmembrane channels linking the cytoplasms of adjacent cells
o Made of proteins called connexons
o Electrically and metabolically couple cells
 Electrically – allow ions to move between cells
 Metabolically – allow small molecules such as nutrients to move between cells
o Called communicating junctions as ions and molecules can move from one cell through
the gap junction proteins (connexons) to another cell
Lecture 1 recording 4: Cell Organelles
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Nucleus:
o Functions: transmission of genetic information to next generation of cells and contains
the information needed for protein synthesis
o Contains:
 Chromatin – DNA and associated proteins
 Nuclear envelope – double layered porous membrane surrounding nucleus
(composed of 2 phospholipid bilayers)
 Nuclear pores – pores in the nuclear envelope that allow molecules to move in
and out of the nucleus
 Nucleolus – site of synthesis of ribosomal RNA
Structure of the Nucleus:
o Nuclear envelope is made of 2 phospholipid bilayers, the inner and outer phospholipid
bilayer
o Nuclear envelope has nuclear pores
 Watery channels made from proteins which allow molecules to move in and out
of the nucleus (DNA too large to pass through the nuclear pores and remains in
the nucleus)
Most Cells Have One Nucleus Except….
o Red blood cells – no nucleus
o Skeletal muscle – many nuclei in one skeletal muscle cell (multinucleate)
Ribosomes:
o Not surrounded by phospholipid bilayer
o Function: protein synthesis
o Composed of a small and large subunit:
 Large and small subunit are not functional when separate
 Large and small subunit join to form a functional ribosome, or one capable of
protein synthesis
 Functional ribosomes may be found free in the cytoplasm or bound to the rough
endoplasmic reticulum (RER) – proteins made in the cytoplasm have a different
final destination in the cell than those made at the RER
Endoplasmic reticulum (ER):
o Fluid filled membranous system
o 2 types: rough (RER) and smooth (SER) endoplasmic reticulum
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 RER – flattened sacs with ribosomes attached to outer surface
 SER – branched tubular structure with no ribosomes attached to outer surface
Functions of the ER:
o RER – synthesizes proteins and performs post-translational modifications needed to
produce a functional protein
o SER – synthesizes lipids, stores calcium (in muscle; called the sarcoplasmic reticulum),
drug detoxification (in liver)
Golgi apparatus:
o Composed of cisternae (flattened sacs)
o Receives vesicles which contain proteins that were made at the RER
o Functions: post-translational modifications of proteins made at the RER, sorts and
packages proteins into vesicles. Proteins in these vesicles may be: secreted from the
cell, become integral membrane proteins, or become proteins of the lysosomes, ER or
Golgi itself
Lecture 1 recording 5: More Cell Organelles
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Lysosomes:
o Contain hydrolytic enzymes which break large molecules into small subunits
o Enzymes are only active at an acidic pH of 5.0 in the lysosome
o Degrade extracellular and intracellular debris (recycle worn out organelles and destroy
bacteria or viruses brought into the cell by fusing with them)
Peroxisomes:
o Contains oxidative enzymes which use oxygen to remove hydrogen from molecules,
breaking them down
o Break down fatty acids, alcohol and drugs
o Abundant in liver and kidney
o Hydrogen peroxide is a by-product of the actions of the oxidative enzymes and is toxic
 Peroxisomes have an enzyme called catalase which breaks down hydrogen
peroxide into water and oxygen
Mitochondria:
o Make ATP or energy – important for cellular respiration, or the process of converting
nutrients into ATP
o Contain double phospholipid membrane (nucleus and MIT are only two organelles with
double phospholipid membrane)
 Outer membrane
 Inner membrane is folded into tubules called cristae
Mitochondria:
o Cells that need more energy have more MIT
o Have own DNA – only organelle other than nucleus to have DNA
Cytoskeleton:
o Non-membrane bound organelle (only ribosomes and cytoskeleton have no
phospholipid bilayer surrounding them)
o Composed of protein filaments or cytoskeletal filaments
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General functions: maintain cell shape, maintain the position of organelles in
the cell, and mediated cell and organelle motility
Cytoskeletal filaments:
o Cytoskeletal filaments include:
 Microfilaments – made of the protein actin
 Intermediate filaments – many different proteins act as intermediate filaments
(intermediate filaments are part of desmosomes)
 Microtubules – made of the protein tubulin
Lecture 2 recording 6: Vesicular Transport
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Vesicular transport:
o Vesicular transport is a form of transport that uses vesicles to move substances across
biological membranes
 Endocytosis – uptake of material into the cell using vesicles containing material
that pinch off from the plasma membrane and enter the cytoplasm of the cell
 3 types of endocytosis – phagocytosis, pinocytosis, receptor-mediated
endocytosis
 Exocytosis – release of material from the cell using vesicles containing material
that fuse with the plasma membrane and release their contents into the
extracellular fluid
Endocytosis and exocytosis:
o Endocytosis – materials are brought into the cell using vesicles
o Exocytosis – materials are released from the cell using vesicles
Phagocytosis and pinocytosis:
o Phagocytosis
 Also called cell eating
 Uses extensions of the plasma membrane called pseudopodia to surround
material being brought up into the cell
 Used for bringing large particles into the cell, such as bacteria or cell debris from
nearby cells
 Process used by white blood cells
o Pinocytosis
 Also called cell drinking
 Plasma membrane simply ‘indents’ below the particles to be brought into the
cell (does not use pseudopodia)
 Plasma membrane pinches together once it has indented and the
vesicle containing particles brought into the cell is called an endocytic
vesicle
 Nonspecific process – simply brings in extracellular fluid and substances
dissolved in that fluid
 Used to ingest small molecules, ions and nutrients (cannot bring in large things
into the cell such as bacteria or cell debris)
o Steps of phagocytosis:
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 Once activated, the phagocytic cell moves to the material it will ingest
 Steps of phagocytosis include:
 Recognition of substance to be ingested
 Attachment of phagocyte to the substance to be ingested
 Pseudopodia reach around substance and come together to form a
phagosome inside the phagocytic cell
 Fusion of the phagosome to a lysosome to form phagolysosome
 Destruction of ingested substance by lysosomal enzymes
 Release of end products into the cell or out of the cell by exocytosis
Receptor-mediated Endocytosis:
o Specific process as it involves receptors which bind specific ligands to be brought into
the cell
o Involves cytoplasmic protein called clathrin
 Binding of ligand to receptor produces conformation change in receptor which
recruits, or causes, clathrin to move to the membrane
 Many receptor-ligand complexes are localized to one area of membrane lined
by clathrin, therefore can concentrate the ligand that is taken into the cell
 The membrane lined by clathrin containing the receptor-ligand complexes
indents and a clathrin coated pit is formed (simply the indented membrane with
clathrin and receptor-ligand complexes)
 A vesicle pinches off containing the receptor-ligand complexes and is lined by
clathrin
 Clathrin is released from the vesicle
 Vesicle may: deposit contents into the lumen of an organelle, travel across the
cell and fuse with plasma membrane to release contents outside cell, fuse with
organelles called endosomes which then sort contents to the Golgi or lysosomes
Receptor-mediated Endocytosis:
o Binding of ligand to receptor recruits clathrin to the membrane
o Many ligand-receptor complexes are found in one area of the membrane, concentrating
the ligand being brought into the cell
o The membrane containing the receptor-ligand complex and lined with clathrin on the
cytosolic surface indents to form clathrin-coated pit
o The pit separates from the plasma membrane to form a clathrin-coated vesicle
Exocytosis:
o The release contents from a cell using vesicles
o Functions: to secrete specific substances (ie. hormones), release waste products, add
components of the membrane, such as lipids and proteins, to the plasma membrane
when vesicles fuse with the membrane. This balances portions of plasma membrane
removed by endocytosis
Lecture 2 recording 7: Driving Forces for Non-vesicular Transport
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Driving Forces for Non-vesicular Transport:
o There are transport process that do not utilize vesicles to move substances across
membranes
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 A difference in energy across a membrane acts as a driving force to move the
substance
 Substances always move from a region of high energy to a region of low energy
if allowed to move passively
 Driving forces can be chemical, electrical or electrochemical
Chemical Driving Force:
o There is a chemical driving force when there is a different concentration of a substance
on either side of a membrane
o Molecules move passively from a high to a low concentration, or ‘down’ the
concentration gradient
o As the side of the gradient increases, the rate of transport of the substance increases
o Chemical driving is due to the concentration gradient of a substance
Electrical Driving Force:
o Any substance that is charged will be affected by the electrical driving force
o The electrical driving force exists due to the membrane potential. Cells in our bodies
have a membrane potential.
o Membrane potential is a difference in the electrical potential or voltage across a cell
membrane
 Also called a ‘separation’ of charge across the membrane
o Any charged substance experiences attractive or repulsive forces due to the membrane
potential. The membrane potential will ‘push or pull’ a charged substance in different
directions, depending on the charge on the substance (ie. positive or negative) and the
membrane potential.
o Electrical driving force is due to the membrane potential
Electrochemical Driving Forces:
o The electrochemical driving force is the sum of the electrical and chemical driving forces
acting on an ion
 Remember: neutral substances are not affected by the electrical driving force
o Direction that the electrochemical driving force acts depends on the net direction of the
electrical and chemical driving forces
Lecture 2 recording 8: Movement of Molecules Across Membranes
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Simple Diffusion:
o Simple diffusion is the passive movement of a molecules through a biological
membrane’s lipid bilayer
 Does not require the input of energy
 How well a substance crosses a phospholipid bilayer depend on the solubility of
the substance in lipid (is it polar or nonpolar) and its size (the smaller the
substance, the more easily it can move between the phospholipids in the
membrane). Remember the membrane is made of phospholipids and has a
nonpolar core due to the presence of the nonpolar fatty acid tails of the
phospholipids
 Polar = water soluble, lipid-insoluble
 Nonpolar = water-insoluble, soluble in lipids
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 Substances that move by simple diffusion move from a region where they are
found in high concentration to a region where they are found in low
concentration, or ‘down’ their concentration gradient
 Which substances move across a phospholipid bilayer by simple diffusion (SD)?
 Substances which are small may move across a membrane by SD, but
have to consider their charge (are they polar or nonpolar or do they
have a charge (positive or negative, like an ion)?
1. If a substance is small, nonpolar and uncharged, it can cross by
SD
2. If a substance is polar and uncharged, it may cross by SD if small
enough
 If a substance is large, uncharged and polar, it will not cross by SD (it
does not have a charge, but being polar and large will not allow it to
cross by SD)
 Any substance that has a charge (positive or negative), regardless of its
size (small or large) cannot cross by SD (For example, ions are very small
but their positive or negative charge will not allow it them interact with
the nonpolar tails of the phospholipids and cross by SD)
Factors Influencing the Rate of Simple Diffusion:
o There are factors which influence the rate of simple diffusion, in addition to the size and
lipid solubility of the substance
 Magnitude of the driving force – the greater the concentration difference of a
substance on either side of the membrane, the greater the magnitude of the
driving force and the greater the rate of SD
 Membrane surface area – how much membrane is available for substances to
cross? A larger cell has a bigger surface area than a smaller cell, and more
molecules of a substance can cross the membrane at one
 Membrane permeability
 The permeability of a membrane to a particular substance depends on
the nature of the transported substance as well as the properties of the
membrane. It depends on:
1. The lipid solubility of the diffusing substance
 Nonpolar substances cross the membrane more readily
2. Size and shape of the diffusing substance
 Small and more regularly shaped substances cross the
membrane more readily
3. Temperature
 At higher temperatures substances move around more,
which will help them diffuse faster across the
membrane
4. Diffusing distance
 This refers to how ‘thick’ the diffusing distance is
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If a substance has to cross more layers of cells, it will
diffuse much slower than if that substance had to cross
only one layer of cells
This is an inverse relationship: a smaller diffusing
distance results in a faster rate of simple diffusion
Osmosis:
(Will be looked at in greater detail in the renal physiology section; know only the basics on
these slides)
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Refers to the net movement of water across a selectively permeable membrane driven
by a difference in solute concentrations on the two sides of a membrane
 Water flows from a region of high water concentration to a region of low water
concentration. This is the same as saying water flows from a region of low solute
concentration to a region of high solute concentration.
 How do we change the concentration of water? We do this by adding a solute.
 Pure water is water with no solute added
 When you add solute, you reduce the “concentration” of water
 Water can move across membranes by simple diffusion (water molecules are
polar but small); the simple diffusion of water across membranes if limited and
finite
 Certain tissues have a larger permeability to water, such as the kidneys
 This is achieved by the presence of water channels called
aquaporins, which water easily moves through
Osmosis:
o Remember: water flows from the solution with the lower solute concentration into the
solution with higher solute concentration
Lecture 2 recording 9: Membrane Transport Proteins and Facilitated Diffusion
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Membrane Transport Proteins:
o The use of a protein to cross the cell is mediated transport
 2 forms of mediated transport: facilitated diffusion and active transport
 Facilitated diffusion
 Passive transport: energy is not required in this process as
substances move passively down their concentration gradient
 Types of proteins involved are carriers or channels
 It is a specific transport process
 Carriers are proteins with specific binding sites for the
substance to be transported across the membrane
 Channels are selective for a specific ion (ie. a sodium
ion) or a type of ion (ie. may allow cations only or
anions only to pass through)
Carrier-mediated Facilitated Diffusion:
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Involves transport proteins called carriers which have a specific binding site for the
substance to be transported
o These proteins bind the substance and move it across the plasma membrane, from a
region of high concentration to a region of low concentration
o Does not require the input of energy, such as ATP
o Example: GLUT family of proteins which are carriers that move glucose across the
membrane from a region of high concentration to a region of low concentration
(glucose is nonpolar and uncharged but it is too large to move across the membrane by
simple diffusion)
Channel-mediated Facilitated Diffusion:
o Channels may be selective for a specific ion or type of ion that moves through them
o Channels do not just allow ions to pass through. For example, aquaporins are water
channels that are specific for water molecules
o The direction and magnitude of ion flux through a channel depends on the
electrochemical gradient of that ion
o Channels exist in an open or closed state and may be gated. Gating refers to the opening
(activation) or closing (by deactivation or inactivation) of ion channels. Gating is the
process of an ion channel transforming between any of its conducting and nonconducting states.
 Channels may be: voltage-gated (changes in voltage cause the channel to open
or close), ligand-gating (the binding of a substance or ligand to a binding site on
the channel causes it to open or close) or mechanically-gated (mechanical
stimuli such as swelling or stretching of a cell causes the channel to open or
close)
Lecture 2 recording 10: Membrane Transport Proteins and Active Transport
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Membrane Transport Proteins:
o The use of a protein to cross the cell is mediated transport
 2 forms of mediated transport: facilitated diffusion and active transport
 Active transport
 Involves transport proteins with specific binding sites for the
substance to be transported
 Capable of uphill transport, or moving a substance against an
electrochemical or concentration gradient from low to high
 Often called pumps
 Utilize energy to mediate uphill transport
 Primary or secondary active transporters obtain energy
from different sources
 Primary active transport
 Energy source to drive the transport process: ATP
 Example: Na+/K+ pump
 Remember: At rest, a cell has a high [Na+]o and
high [K+]i. (o= outside the cell; i=inside the cell)
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Na+/K+ pump moves 3 Na+ ions out of the cell
and 2 K+ ions into the cell for every molecule of
ATP hydrolyzed. This pump moves Na+ and K+
ions against their concentration gradients.
 Functions of pump: contributes to establishing
and maintaining the membrane potential of the
cell and maintains the Na+ and K+ concentration
gradients
 Secondary active transport
 Energy source to drive the transport process:
movement of an ion down its electrochemical gradient
 Couples movement of an ion down its electrochemical
gradient with that of an another substance moving
against its concentration gradient
 Example: Na+/glucose cotransporter or Na+/H+
exchanger. In both cases Na+ moving down its
electrochemical gradient provides the energy to move
H+ or glucose against its electrochemical (H+) or
concentration gradient (glucose)
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Transport Rates:
 Simple diffusion: unsaturable transport process as it does not involve proteins
and binding sites; as you increase the concentration of the substance, you
increase the movement of substance across the membrane
 Mediated transport: saturable transport process as it involves proteins and
binding sites; each cell has a limited number of proteins and each protein has a
limited number of binding sites for a substance. As the concentration of
substance increases, an increased number of binding sites are occupied. The
transport rate will plateau, or stop increasing, once all sites are occupied; at this
point further increasing the concentration will not further increase the transport
rate.
Lecture 3 recording 11: Signal Transduction
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Chemical Messengers:
o A form of intercellular communication; intercellular – “between cells”
o May be lipid-soluble or lipid-insoluble
o Used for the process of signal transduction, which is the sequence of events between
the binding of a messenger to a receptor and the production of a cellular response
Properties of Receptors:
o Receptors have specific binding sites for a specific messenger
o Receptors show saturation, in that they have a defined number of binding sites for a
messenger (a single receptor may have only 1 or 2 binding sites for a messenger)
o Receptors bind different messengers with different affinities. Affinity refers to how
strong a receptor and messenger bind; high affinity means they bind very strongly a low
concentrations while low affinity means that the interaction between messenger and
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receptor is weaker and it requires higher concentrations of a messenger to bind. Some
receptors bind a particular substance with high affinity while other receptors bind to
their substance with low affinity.
o Receptors may be found on the plasma membrane or intracellularly, in the cytosol or in
the nucleus
Intracellular receptors:
o These receptors are found inside the cell, in the cytoplasm or in the nucleus
o Lipid-soluble chemical messengers diffuse across the plasma membrane and bind to
intracellular receptors
o Example of chemical messengers that bind to intracellular receptors: steroid hormones
(hormones derived from cholesterol)
o Chemical messengers which bind to intracellular receptors act as transcription factors
 Transcription factors alter the rate of transcription of mRNA in the nucleus by
binding to a response element
 A response element is a specific sequence of DNA near the beginning of a gene.
By binding to the response element, a chemical messenger can alter the rate of
transcription of a gene, which will alter the rate of translation of the mRNA into
a protein (each gene contains the instructions for producing a specific protein)
 Transcription factors alter the rate of protein synthesis
Lecture 3 recording 12: Membrane-bound Receptors
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Membrane-bound Receptors:
o Chemical messengers that are water-soluble (hydrophilic; lipid-insoluble) cannot diffuse
across the hydrophobic core of the plasma membrane; bind to receptors on the
extracellular surface of the plasma membrane
 Examples include peptide or protein hormones
 3 types of membrane-bound receptors are channel-, enzyme-, or G-proteinlinked receptors
o Important definitions:
 First messenger – extracellular chemical messenger that binds to a specific
membrane-bound receptor
 Second messenger – a substance that enters or is generated in the cytoplasm of
a cell following the binding of the first messenger to its receptor
 Protein kinase – an enzyme that phosphorylates another protein, or adds
phosphate groups to the protein. By adding phosphate groups to a protein, a
protein kinase alters the activity of another protein
Receptors That Are Ligand-gated Ion Channels:
o A membrane-bound receptor
 This receptor (a protein) has a receptor component with binding sites for a
chemical messenger and an ion channel component. It is one protein that
functions both as a receptor and an ion channel.
 Steps of signal transduction:
1. A first messenger binds to binding sites on the receptor
2. An ion channel in the receptor protein opens
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3. Ions move through the channel. As the ions have a charge, they alter
the electrical properties of the cell and produce a response.
 This is a fast process as the receptor and ion channel are a single protein
 The channel in the receptor may be a calcium channel. Calcium has many roles
in the cell.
Receptors That Function As Enzymes:
o A membrane-bound receptor
 This receptor (a protein) has a receptor component with binding sites for a
chemical messenger and intrinsic enzyme activity (intrinsic = within the receptor
protein)
 Also called receptor tyrosine kinases: the enzyme part of the
receptor is a kinase that phosphorylates tyrosine amino acid
residues (ie. adds phosphates to tyrosine amino acid residues)
 The tyrosine kinase part of receptor autophosphorylates or
phosphorylates tyrosine amino acid residues on the
receptor (auto = self)
 The phosphorylated tyrosines (phosphotyrosines) on the
receptor act as docking sites for proteins in the cytoplasm of
the cell
 Once a protein binds to the phosphotyrosines it is activated
by phosphorylation, and will bind to other proteins in the
cell to eventually produce a response
Lecture 3 recording 13: More Membrane-bound Receptors
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Membrane-bound Receptors:
o G-protein linked receptor: membrane-bound receptor that binds extracellular chemical
messengers
G-protein Linked Receptors:
o G-proteins
 Found at the cytosolic surface of the plasma membrane
 Bind guanosine nucleotides (GDP or GTP), and this is why they are called Gproteins (G= guanosine)
 A protein made of 3 subunits called alpha, beta and gamma
 Function as a link between the receptor in the plasma membrane and an
effector protein, which is an ion channel or an enzyme
 Both the receptor and the effector protein interact with the Gprotein
 Only the alpha subunit of the G-protein binds to GTP or GDP, not the beta and
gamma subunit
G-protein Linked Receptors: An Animation:
(This slide contains an animation which will be looked at in detail in later slides)
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G-protein Linked Receptors:
o Alpha subunit of the G-protein: binds the guanosine nucleotides GDP and GTP
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 Alpha subunit: when inactive binds GDP
 Alpha subunit: which active binds GTP
Binding of an extracellular first messenger to a membrane-bound receptor causes a
conformational change in that receptor, altering the affinity of the alpha subunit of the
G-protein for GDP
 The affinity of the alpha subunit for GDP decreases and the affinity for GTP
increases; the alpha subunit releases GDP and binds GTP
The G protein will now dissociate from the receptor and the GTP-bound alpha subunit is
activated and separates from the beta and gamma subunits
The activated alpha subunit moves to its target protein in the membrane, called the
effector protein.
 Effector protein is either an enzyme or an ion channel
 The GTP-bound alpha subunit will alter the activity of this effector protein to
produce a response in the cell
The activated alpha subunit hydrolyzes, or breaks down, the GTP to GDP and inorganic
phosphate, returning itself to the inactive state in which it is bound to GDP. The alpha
subunit recombines with the beta and gamma units, which anchor the alpha in the
membrane.
The G-protein with the 3 subunits (alpha, beta and gamma) then recombines with the
receptor
Lecture 3 recording 14: G-proteins and Second Messenger Systems
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Actions of G-proteins on Ion Channels:
o How does binding of a first messenger alter the activity of an effector ion channel?
1. Binding of first messenger to receptor causes conformational change in receptor
2. Affinity of α-subunit for GTP increases; GDP dissociates, GTP binds
3. GTP-bound α-subunit dissociates from β and γ; moves to ion channel
4. Ion channel opens or closes (depending on state of channel prior to binding of
GTP-bound α-subunit), alters flow of ions across membrane
Actions of G-proteins on Enzymes:
o How does binding of a first messenger alter the activity of an effector enzyme?
1. Binding of first messenger to receptor causes conformational change in receptor
2. Affinity of α-subunit for GTP increases; GDP dissociates, GTP bind
3. GTP-bound α-subunit dissociates from β and γ; moves to enzyme
4. There are different types of G-proteins:
 If the G-protein is a Gs protein, it stimulates or activates the enzyme (S=
stimulatory); if the G-protein is a Gi protein, it inhibits the enzyme (I=
inhibitory)
5. Altering the activity of the enzyme alters the production of a second messenger
by the enzyme in the cytosol
cAMP Second Messenger System:
o cAMP second messenger system – most common second messenger system found in
the cells in our body
 cAMP = a second messenger
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Steps involved in the production of cAMP:
1. Binding of a first messenger to a receptor causes a conformational change in the
receptor. This increases the affinity of the alpha subunit for GTP; GTP binds after
the release of GDP.
2. The activated alpha subunit of the Gs protein separates from the beta and
gamma subunits and moves to and binds to adenylyl cyclase, activating it.
 Adenylyl cyclase is a membrane-bound enzyme
 A stimulatory G protein or GS stimulates or activates adenylyl cyclase
3. The catalytic site of adenylyl cyclase is located on the cytoplasmic surface of
the plasma membrane; adenylyl cyclase catalyzes the conversion of cytosolic
ATP molecules into cyclic AMP.
4. Cyclic AMP acts as a second messenger and diffuses through the cytoplasm
5. cAMP binds to and activates protein kinase A (PKA), which is also called cyclicAMP-dependent protein kinase.
 PKA requires cAMP to activate it
6. Activated PKA catalyzes the phosphorylation of proteins in the cell by
transferring a phosphate group from ATP to cellular proteins
7. Once these cellular proteins have been phosphorylated, their activity is
altered, resulting in a cellular response
cAMP Second Messenger System: An Animation:
(This slide contains an animation which looks at the cAMP second messenger system)
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Calcium as a Second Messenger:
o Calcium may act as a second messenger in cells
o Calcium normally found in low concentrations in the cytoplasm
o Calcium may enter the cell from the extracellular fluid following the binding of a first
messenger to a receptor
 The receptor may be a receptor that is a ligand-gated ion channel, in which case
the intrinsic ion channel opens and allows calcium to move into the cell. The
receptor may be a G-protein linked receptor, which will open a calcium channel
in the membrane. With either receptor, calcium enters the cell and its
concentration increases in the cytoplasm.
o The increase in calcium levels in the cytoplasm is not enough to produce a response in
the cell; calcium that has entered the cytoplasm from the ECF will bind to receptors on
an organelle called endoplasmic reticulum (the ER may store calcium; it has a high
concentration of calcium). Binding of calcium to receptors on the ER causes calcium to
be released from the ER, further increasing levels in the cell; this is called calciuminduced calcium release as calcium entering the cell from the ECF causes its own release
from the ER into the cytoplasm.
o Calcium now acts as a second messenger
o Calcium activates calmodulin, a cytosolic protein that is normally found inactive in the
cell; calmodulin requires calcium to activate it
o Active calmodulin activates a calmodulin-dependent protein kinase
o The protein kinase phosphorylates proteins in the cell, producing a response