Transport of Substances through the
cell membrane
+
Na
K+
Ca2+
Mg2+
ClHCO3Phosphates
SO4Glucose
Protein
Amino Acids
Extracellular
143 mmol/l
4 mmol/l
2.5 mmol/l
1.2 mmol/l
103 mmol/l
28 mmol/l
4 mmol/l
1 mmol/l
4.5-5 mmol/l
60-80 g/l
1.7 mmol/l
Intracellular
10 mmol/l
140 mmol/l
0.001 mmol/l
58 mmol/l
4 mmol/l
10 mmol/l
75 mmol/l
2 mmol/l
0-1.1 mmol/l
11.1 mmol/l ?
The lipid bilayer, which is the cell membrane, is not miscible with either the extra cellular or the
intracellular fluid. This means the lipid bilayer constitutes a barrier against water and water soluble
substances, but lipid soluble substances are able to cross this barrier.
Transport Proteins constitute a pathway across the membrane. (for example water soluble
substances)
1.) Channel Proteins: Have watery spaces all the way through the membrane and allow free
movement of water and selected ions or molecules.
2.) Carrier Proteins:
Bind with molecules or ions, then undergo a conformational change and
then move the substance through the membrane
The Transport of substances occurs in two ways:
1.) Diffusion
2.) Active Transport
Diffusion: - Random molecular movement of substances, molecule by molecule, either through
intermolecular spaces in the membrane or in combination with a carrier protein.
- the energy that causes diffusion is the energy of normal kinetic motion of water
- all molecules and ions in the body are in constant motion  “heat”
↘ this motion never stops except at ABSOLUTE ZERO temperature
↘ If the molecules collide the energy gets transferred.
“The continual movement of molecules among one another in liquids and gases is
called diffusion”
Diffusion through the cell membrane is divided into two subtypes:
① Simple Diffusion
↘ the kinetic movement of molecules and ions occurs through a membrane
without any interaction with a carrier protein
↘ the rate of diffusion is determined by the amount of substance available,
the velocity of kinetic motion and the number and size of openings in the
membrane
↘ can occur in 2 ways:
① Diffusion of lipid soluble substances:
↘ The rate of diffusion of these substances is directly
proportional to its lipid solubility. Ex.: Alcohol, Oxygen, nitrogen,
CO2
② Diffusion of water and other lipid insoluble molecules:
↘ through channel proteins (pores)
↘ lipid insoluble molecules can pass through the protein pore
channels in the same way as water molecules, if they are water
soluble and small enough
Diffusion though Protein Channels and “gating” of these Channels
↘ Protein channels are distinguished by two characteristics:
① Selective Permeability of Protein Channels
↘ results from the characteristic of the channel:
ex diameter, shape and the nature of the electrical
charges and chemical bonds along its inside
surface
Ex.: Sodium Channel:
↘ only 0.3-0.5 nm in diameter
↘ inner surface of channel is strongly
negatively charged (these charges can
pull hydrated Na+ ions inside the
channel)
↘ Sodium ions diffuse in either
direction according to the usual laws of
diffusion
Ex.: Potassium Channel:
↘ smaller than sodium channels
↘ only 0.3 nm in diameter
↘ inner surface of channel is not
negatively charged
↘ The smaller hydrated potassium ions
can easily pass though these small
channels
② Gating of Protein channels
↘ controls the permeability of channels
① Voltage Gating:
↘ The molecular conformation or the
chemical bonds of the gate depends on
the electrical potential across the
membrane.
Ex.: Sodium Channels
↘ If the inside of the cell is
negatively charged the
outside gate is closed, but if
the inside gets less negative
(by an Action Potential for
example) the Gate opens and
lets Sodium Ions into the cell.
Ex.: Potassium channel
↘ Potassium gates are on the
intracellular end of the
channel
↘ open when the inside of
the channel becomes
positively charged
↘ responsible for terminating
the APs
② Ligand (chemical) gating
↘ The Gate is opened or closed by
binding to a ligand. This causes the
conformational or chemical bond to
change so that the channel is either
opened or closed
Ex.: Acetylcholine channel
↘ Acetylcholine opens this
channel, providing a
negatively charged pore with
a diameter of about 0.65 nm
↘ Allows uncharged
molecules and positively
charged ions smaller than
that diameter to pass through
↘ important in nerve signal
transduction
↘ the diffusion in simple diffusion through an open channel increases
proportionately with the concentration of the diffusion substance
② Facilitated Diffusion
↘ carrier mediated diffusion
↘ rate of diffusion reaches a max called Vmax
↘the rate of diffusion depends on how fast the carrier protein can undergo
conformational changes
↘ glucose and most amino acids cross the cell membrane via facilitated
diffusion
Factors affecting the net rate of diffusion:
1.) Concentration difference:
a. The Rate at which the substance diffuses inward is proportional to the
concentration of molecules on the outside (higher concentration on the outside)
b. Net Diffusion (Co-Ci) |(Co= Concentration outside; Ci= Concentration inside)
2.) Membrane electrical potential
a. If an electrical charge is applied across a membrane, the electrical charges of the
ions cause them to move through the membrane even though no concentration
difference exists
𝐶
b. Nernst Equation: 𝐸𝑀𝐹 = ±61 log 𝐶1 |EMF= Electromotive Force (voltage) in
2
millivolts; C1=Concentration on side 1; C2=Concentration on side 2
c. Important values:
Na+
+60 mV
+
K
-90 mV
Ca2+
+130 mV
Cl-95 mV
3.) Pressure Difference
a. Occurs for example in blood capillary membranes
b. “Pressure is the sum of all forces on the different molecules striking a unit
surface area at a give instant”
c. Molecules move from the area of high pressure to the area of lower pressure
Osmosis across selectively permeable membranes – “Net Diffusion of Water”
-
Most abundant substance that diffuses through cell membranes is water
Normally the amount of water that diffuses across a membrane is the same in both
directions  net movement is zero
A concentration shift in solute causes the equilibrium to shift in the direction that favors
the stress  from low to high concentration.
“Net movement of water caused by a concentration difference of water is called
Osmosis”
Osmotic Pressure is the pressure which is needed in order to stop osmosis.
Active Transport
-
Required to retain a concentration gradient
Example: Na+ - K+ Pump
Active transport can be divided into two types according to the soured of energy:
1. Primary active transport – energy is derived from the breakdown of adenosine
triphosphate (ATP)
2. Secondary active transport – energy is derived secondarily from energy that has
been stored in the form of ionic concentration difference of secondary molecular
-
of ionic substances between the two sides of the cell membrane.  created by
primary active transport!
Examples of primary active transport:
o Sodium Potassium Pump
 Pumps 3 Na+ outwards and 2 K+ inwards
 Establishes a negative electrical voltage inside the cell
 Carrier Protein is made up of a α and a smaller β subunit
 β subunit has unknown function
 α subunit has 3 specific features:
 has 3 receptor sites for Sodium on the inside
 has 2 receptor sites for Potassium on the outside
 the inside portion of this protein near the sodium binding sites
has ATPase activity
 Function of the Na+-K+ Pump:
 When potassium and 3 sodium ions bind to their binding sites of
the carrier protein, ATPase becomes activated  cleaves one
ATP molecule into ADP and liberating a high energy phosphate
bind  this liberated energy causes a chemical and
conformational change in the protein  sodium goes out and
potassium goes in.
 Sodium – potassium pump keeps the cell from bursting (activates
osmosis)
 Na+-K+ Pump is said to be electrogenic because it breates a positive
charge on the outside and a negative charge on the inside
o Calcium Pump:
 Calcium is kept in low concentration in the intracellular cytosol:
 2 Ca2+ Pumps:
o Located in the cell membrane; pumps Ca2+ ions to the
outside
o Pumps Ca2+ ions into the intracellular vesicular organelles
(for example sarcoplasmic reticulum of muscle cells and
mitochondria in all cells)
o Primary active transport of Hydrogen ions
 Very important in2 places of the body
 Gastric glands
 Late distal tubules and cortical collecting ducts
Secondary Transport – Co Transport and Counter Transport.
-
-
Due to the transport of Na+ ions out of the cell a concentration gradient of Na+ ions
across the membrane develops (high concentration on the outside and low
concentration on the inside)
The concentration gradient is a storehouse of energy because Na+ ions tend to diffuse
o Gives energy for 2 types of secondary active transport:
 Co-Transport:
 Sodium pulls other substances with it during diffusion


Coupling mechanism is required; this is achieved by a carrier
protein in the cell membrane
 Carrier protein serves as attachment point for Na+ and the
substance to be co-transported  once they have attached, the
energy gradient of sodium causes both substances to diffuse
across the membrane
 Examples:
o Na+ - Glucose Co-transport
o Na+ Co-transport of proteins
Counter Transport:
 Na+ binds to a carrier protein on the exterior while the other
substance binds to the interior side of the same protein 
conformational change occurs and energy released by the
sodium ion moving to the interior causes the other substance to
move to the outside.
 Examples:
o Na+ - Ca2+ Counter transport
o Na+ - H+ Counter transport