BMED 2801 – Lecture 10: Membrane ionic gradients
Describe the characteristic arrangement of the soma, axon, dendrites and axon terminal of a
somatic motor neuron and explain the roles that these structures play in the function of the
neuron.
Model: Somatic motor neuron: are efferent neurons (conveying information away from the CNS) that
control skeletal muscles
Soma (cell body):
Arrangement- Resembles the typical cell  has a nucleus, and all organelle (mitochondria + golgi apparatus)
needed to direct cellular activity
- Voltage gated sodium channels are located at soma
- It has an extensive cytoplasm that extends outwards into the axon and dendrites
- The position of the cell body varies in different types of neurons
- In most neurons the cell body is small (generally making up 1/10th or less of the total cell vol.)
Role in the function of the neuron- Integration center of the neuron  where the signals from the dendrites are joined and passed
on.
- The soma and the nucleus do not play an active role in the transmission of the neural signal.
- Instead, these two structures serve to maintain the cell and keep the neuron functional  Posses
cellular machinery to make essential proteins vital to cellular function
- Injured somatic motor neuron (axons severed from soma) = degeneration of the distal portions of
the neuron  resulting in permanent paralysis of the muscles innervated by the neuron.
Dendrite:
Arrangement- thin branched processes – increasing the surface area of the neuron  to allow for
communication with multiple neurons
- The simplest neurons have only a single dendrite – other extreme e.g. neurons in the brain –
have dendrites with incredibly complex branching.
- The dendrite’s surface can be expanded further by the presence of dendritic spikes.
Role in the function of the neuron- Receives excitatory inputs
- In the PNS – dendrites function to receive incoming information from neighboring cells and
transfer it to the integrating region of the neuron.
- In the CNS – dendritic spikes can function as independent compartments – sending signals back
and form with other neurons in the brain.
Axon:
Arrangement- Most neurons have a single axon – origination from the axon hillock (a specialised region on the
cell body)
- axon vary in length
- They often branch along their length – forming collaterals (axonal branches)
- Each collateral ends in a swelling called the axon terminal.
Role in the function of the neuron-
transmit outgoing electrical signals from the integration center of the neuron to the end of the
axon (axon terminal)
At the distal end the electrical signal is transmitted into a chemical signal by secretion of a
neurotransmitter, neuromodulator or neurohormone.
Axon terminal:
Arrangement:
- Axon terminal contains – mitochondria + membrane bound vesicles filled with neurocrine
molecules
Role in the function of the neuron-
The axon terminal  is the point where electrical signals are translated into a chemical signal 
in the form of neurocrine molecules.
A Neurocrine mol. that diffuses across extracellular space and has:
A rapid effect – it is called a neurotransmitter
Acts more slowly as an autorine or paracrine signal – is called a neuromodulator
Or neurocirne that diffuses into the blood for distribution – is called a nerohormone
Draw a diagram illustrating the general structure of the plasma membrane. Label phospholipids,
intrinsic (trans-membrane) proteins and extrinsic proteins and polysaccharides (carbohydrate
chains). Include in this drawing an ion channel.
Transmembrane
Lipid anchored
proteins
The Fluid mosaic model
The Phospholipid bilayer
Consists of:
• Bipolar phospholipids
• Hydrophilic – glycerol-phosphate head groups (face water) - polar
• Long hydrophobic- fatty acid tails (oily interaction) – non polar
 hydrophilic phosphate heads face the inside and outside of the cell, and the hydrophobic lipid tails
are hidden in the center of the membrane
• The structures are self assembling and stable
• The lipid bilayer is a barrier to large, charged, polar molecules
 It generally allows for the passive diffusion of hydrophobic molecules
Lipid bilayer is modified by addition of:
- Carbohydrate chains - attach to membrane proteins (glycoproteins) or to membrane lipids
(glycolipids) – forming a protective layer, known as glycocalyx.
Intrinsic/integral/transmembrane proteins (eg channels, transporters, receptors)  recognise
and respond to molecules or to changes in the external environment.
Membrane-attached proteins (eg cytoskeleton-linking proteins)  hold the cytoskeleton, the
cell’s interior structural scaffolding, in place to maintain cell shape
Specialised lipids & glycolipids on the extracellular surface
- Cholesterol, which is mostly hydrophobic, insert themselves between the hydrophilic heads of the
phospholipids helps, makes the membrane impermeable to small water-soluble molecules.
• Channels and transporters selectively modify permeability of membrane
Explain how hydrophobic and hydrophilic forces may lead to the formation of the fluid mosaic
model of the lipid bilayer. What is on either side of the lipid bilayer and how does it stabilise the
bilayer?
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On either side of the lipid bilayer lie the extracellular and intracellular fluid. 
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All the molecules in the bilayer are in a low energy state, so are stable on a molecular level.
The layer is kept stable because the phosphate head is attracted to the extracellular and
intracellular fluid on either side while the lipid is repelled.
This lines up the molecules – the hydrophilic head pulling towards the extra/intracellular fluid and
the tail repelling and opposing the pull of the hydrophilic head away from the fluid. They have no
reason to move. In a bilayer, the molecules are back to back, so lipids are trapped in a
hydrophobic section.
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How are the membrane proteins attached to the lipid bilayer?
- membrane proteins are classified in 3 categories
- Integral/transmembrane proteins, peripheral proteins and lipid-anchored proteins.
transmembrane proteins
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Are tightly bound to the nonpolar 20-25 amino acids in the alpha-helix segments that pass
through the bilayer.
These hydrophobic amino acids create noncovalent interactions with the lipid tails of the
phospholipids in the membrane bilayer.  Results in the transmembrane protein being tightly
bound into the membrane.
Peripheral proteins
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Attach loosely to the transmembrane proteins or the polar heads of the phospholipids.
Lipid – anchored proteins
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Are covalently bound to the lipid tail.
The lipid bilayer is a selectively permeable membrane. What kind of substances can permeate the
lipid bilayer and why?
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There are 2 properties of particles that influence whether they can permeate through a plasma
membrane w/o any assistance:
1. The relative solubility of the particle in lipid
2. Size of the particle – very small molecules can pass through the gaps of the bilayer.
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Highly lipid soluble particles can dissolve into the lipid bilayer and pass through the membrane
Uncharged or non-polar molecules e.g. O2, CO2, and fatty acids – are highly lipid soluble and
readily pass through the membrane.
Charged particles such as (Na+ & K+) and large polar molecules (glucose and proteins) have low
lipid solubility and thus can not penetrate through the membrane without aid.
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Diffusion:
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The movement of molecules from an area of high concentration to an area of lower concentration
of the molecule(s)
It is a passive process – using only the kinetic energy possessed by all molecules.
Lipophilic Molecules Diffuse through the phospholipid bilayer
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Diffusion directly across the phospholipid bilayer is called simple diffusion. The rate of diffusion
depends on the ability of the diffusing molecule to dissolve in the lipid layer of the membrane.
Only non polar molecules that are lipophilic traverse the central lipid core.
As a rule only lipids steroids and small lipophilic molecules move across the membrane through
simple diffusion.
One important exception is water- water although polar may diffuse slowly across the membrane
(membranes with high cholesterol content are less permeable to water).
The rate of diffusion is dependent on the magnitude of the concentration gradient – the greater
the concentration difference, the faster the diffusion.
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The rate of diffusion depends on the ability of the diffusing molecule to dissolve in the lipid layer
of the membrane (how permeable the lipid layer is to the diffusing molecule)
The rate of diffusion is directly proportion to the surface area of the membrane- the larger
membrane surface area (SA) the more molecules can diffuse across per unit time.
The rate diffusion is inversely proportion to thickness of the membrane- the thicker the
membrane, the slower the rate.
Fick’s Law of Diffusion:
Rate of diffusion α Surface area x Concentration gradient x Membrane permeability
Membrane thickness
Membrane permeability is influenced by
1) The size of the diffusing molecule-as molecule size increases, membrane permeability
decreases
2) The lipid solubility of the molecule-as lipid solubility increases membrane permeability
increases
3) The composition of the lipid bilayer-more cholesterol molecules = decrease in membrane
permeability.
In most physiological cases membrane thickness is constant, therefore we can rearrange:
Diffusion rate = concentration gradient x membrane permeability
surface area
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This equation describes the flux (diffusion rate per unit SA) of the molecule.
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Flux= concentration gradient x membrane permeability.
For substances that cannot diffuse across the lipid bilayer there are:
• Active transport- membrane proteins that use energy to force substance UP its concentration gradient
• Facilitated Diffusion-facilitate a substance diffusing across the membrane molecule by molecule
• Diffusion channels eg water channels and ion channels
Describe a key difference between the way an ion channel allows ions to cross a membrane and
the way a facilitated transporter protein works
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The vast majority of solutes (lipophobic or electrically charged) cross membranes with the help of
membrane proteins- a process we call a mediated transport.
Protein mediated transport is carried out by two groups of proteins: transporters and receptors.
Transporters:
- Membrane transporters move molecules across membranes.
- There are two types
1) Channel proteins- create water filled passage ways that directly link the intracellular and
extracellular compartments
2) Carrier proteins- Bind to the substrates that they carry but never form a direct connection between
the intracellular fluids and extracellular fluid (carriers are open to one side of the membrane or the
other, but not to both).
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Channels proteins allow more rapid transport across the membrane but are not as selective.
Carrier proteins, whilst slower, are selective and can move larger molecules than channels can.
The key difference between ion channels and facilitated diffusion:
- Ion channels are formed by channel proteins
- Facilitated diffusion is mediated by carrier proteins  slower but more specific
Ion channel
Channel proteins form open, water filled passage ways (ion/water channels)
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Are made of membrane spanning protein subunits that create a cluster of cylinders that surround
a narrow, water filled pore.
Movement through channel is restricted primarily to water and ions.
Channels proteins are named according to the substance they allow to pass. e.g. water channels,
Na+ channels, K+ channels and non specific monovalent cation channels that transport Na+, K+,
Li+.
The selectivity of a channel is determined by the diameter of its central core and by the electrical
charge of the amino acids that line the channel.
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If the channels amino acids are positively charged, positive ions will be repelled and negative ions
will be passed through.
The opened or closed state of a channel is determined by the regions of the protein molecule that
act like swinging gates. Channels can be classified according whether their gate are usually
opened or closed.
Open channels = gate open- allowing ions to move back and forth without regulation. (Aka leak
channels or pores). Gated channels= closed state- allows these channels to regulate the
movement of ions.
Gated channels are controlled by intracellular messenger molecules or extracellular ligands.
(Chemically gated channels), by the electrical state of the cell (voltage gate channels), or by a
physical change e.g. increased temp. Or tension on the membrane that pops the channel open
(mechanically gated channels).
Facilitated diffusion
- Passive protein mediated transport that moves molecules down the concentration gradient- net
transport is stopped when concentrations are equal.
- no outside energy source is needed  Facilitated diffusion is driven by the chemical driving force
acting on the substance
- Involves a carrier protein that can shepherd a large/polar/charged molecule across the lipid
bilayer

Carrier proteins bund with specific substrate and carry them across the membrane by changing
the conformation
 The conformation change required of a carrier protein makes this mode of transmembrane
transport much slower.
 Carriers form passageways, but these opening are never open to both sides at the same time.
Explain the difference between primary and secondary active transport and give an example of
how they may work together in some cells.
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Active transport is a form protein mediated process, requiring energy from ATP or another outside
source
It involves moving molecules against their concentration gradients- i.e. from areas of lower
concentration to areas of higher concentration = disequilibrium.
Primary active transport
• Primary active transporter proteins use the energy of the high-energy phosphate bond of ATP to force
molecules or ions UP their concentration gradient
• The energy is supplied by hydrolysis of the phosphate bond on ATP
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Primary active transporters are known as ATPase  these are enzymes that hydrolyze ATP to
ADP and inorganic phosphate, releasing usable energy in the process.
ATPase are sometimes called pumps e.g. Na+-K+ ATPase (sodium-potassium pumps)
Primary Active transport exampleNa+/K+ Pump
 In healthy cells the cytoplasmic concentration of K+ is high (~120mM) while the concentration of
Na + is low (~10mM)
 The Na+/K+ Pump (Na+/K+ ATPase) is responsible for maintaining this concentration gradient
over a time frame of minutes to hours
Secondary active transport
• Secondary active transporter proteins use potential energy stored in the concentration gradient of one
molecule to drive another molecule UP its concentration gradient
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All secondary active transport ultimately depends on primary active transport – because the
concentration gradients that drive secondary transport are created using energy from ATP first.
The most common secondary active transport systems are driven by the sodium concentration
gradient (higher conc. of Na+ in extracellular fluid, low conc. inside the cell).  As a Na+ moves
into the cell, it wither brings one or more molecules with it or trades places with molecules exiting
the cell.
e.g.
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Na+/glucose co-transporter (glucose import driven by the Na+ conc.gradient, in turn maintained
by the Na+/K+ pump)
In this secondary active transport process – both Na+ and glucose bind to the SGLT protein on
the extracellular fluid side
the sodium first bunds and causes a conformational change that creates a high-affinity binding
site for glucose
When glucose binds to SGLT, the protein changes conformation again and opens its channel tot
eth intracellular fluid.
Sodium is released s it moves down its concentration gradient, the loss of Na+ from the protein
changes the biding site for glucose back to low-affinity and glucose is released.
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Both types of active transport working together work similar to that of facilitated diffusion --. That
is a substrate to be transported binds to a membrane carrier and the carrier that changes
conformation, releasing the substrate into the opposite compartment.
Explain osmosis in terms of the forces acting on water molecules and the significance of osmosis for
mammalian cells.
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Osmosis – the movement of water across a membrane in response to a solute concentration
difference.  the diffusion of a solvent through a semi permeable membrane from a dilute to a
more concentrated solution
The distribution/concentration of solutes depends on whether a substance can cross the cell
membrane.
Osmotic equilibrium – vital for cells and most imp. Molecule in the human body– since it is a
solvent for all living mater + body = aprox 60% water.
Explain the term chemical driving force. Why is the chemical driving force on an ion or molecule important
in terms of cellular function.
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The chemical driving force is the difference in the concentration gradient, resulting in a potential
energy.
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The chemical driving force is impt – because for example – the sodium ion concentration
gradient, where Na+ concentration is high in the extracellular fluid and low inside the cell  is a
source of potential energy that the cell can harness for other functions
E.g. nerve cells use the sodium gradient to transmit electrical signals, and epithelial cells use it to
drive the uptake of nutrients, ions and water.
Also secondary active transport- involved membrane transporters using this potential energy to
transport molecules across the plasma membrane.
Sodium, Potassium and calcium ions are not evenly distributed across the plasma membrane of healthy
cells. Outline how the intracellular and extracellular concentrations differ for each.
Sodium ions are concentrated in the extracellular fluid
Potassium ions are concentrated in the intracellular fluid
Chloride ions are concentrated in the extracellular fluid but in lower concentrations than sodium ions.
How do the differences in sodium and potassium ion concentration gradients come about?
- Differences in sodium and potassium gradients result from the permeability characteristics of the
cell membrane.
- There is a higher concentration of Na+ immediately outside the cell membrane and a higher
concentration of K+ immediately inside the cell.
- These concentrations are maintained by the Na+/K+ pump.