Download Concentration gradient

Solutions
• The ICF and the ECF are homogeneous mixtures of
substances including water, ions, amino acids,
disaccharides, triglycerides… called solutions
• Solutions are divided into 2 parts
– Solvent
• substance present in greatest amount
• the solvent of the body is water
– Solute(s)
• substance(s) present in lesser amounts
• every other substance in the body is a solute
– ions, carbohydrates, proteins, fats, nucleotides…
• Solutions are described in terms of their concentration
– the amount of solutes in a given volume of solution
• Units include: molarity, %, weight per volume
ECF vs. ICF
• The concentration of individual solutes is different
– the cell membrane transports and separates each solute between the
ICF and ECF to maintain optimal working conditions within the
ICF
• The total solute concentration of the ECF = ICF
– prevents the cell from swelling or shrinking
INTRACELLULAR
EXTRACELLULAR
Major cations:
Na
K
+
+
Mg
++
Major anions:
Cl
-
HCO 3 Protein
Phosphates
SO
-4
Org. acids
150
100
50
Concentration (mM)
0 0
50
100
Concentration (mM)
150
Modes of Membrane Transport
• Vesicular Transport
– use vesicles to move substances into/out of the cell
– transport of substances that are TOO LARGE to move
through a membrane
• movement of few very large substances
– cells, bacteria, viruses
• movement of very many large molecules
– proteins
• Transmembrane Transport
– movement of small molecules through a membrane
• plasma membrane, Golgi membrane, ER membrane,
lysosome membrane…
– ions, fatty acids, H2O, monosaccharides, steroids,
amino acids…
Vesicles
• “Bubbles” of phospholipid bilayer membrane with
substances inside
– typically proteins
– substances DO NOT contact the cytosol
• Created from a membranous organelle by the “pinching” or
“budding” of the membrane
• Can “fuse” (merge) with a phospholipid bilayer membrane
Vesicular Transport - Exocytosis and Endocytosis
• Exocytosis
– moves substance out of the cell
• Endocytosis
– substances are moved into the cell by trapping them in a
vesicle
• cell membrane creates pseudopods (“false feet”)
Exocytosis of Proteins
Exocytosis
Types of Endocytosis
• Phagocytosis
– “cell eating”
– endocytosis of few very large substances (bacteria,
viruses, cell fragments)
– vesicles containing cells fuse with lysosomes which
digest the cells
• Pinocytosis
– “cell sipping”
– endocytosis of extracellular fluid
• Receptor-mediated endocytosis
– endocytosis of a specific substance within the ECF
– requires that the substance attaches to the extracellular
portion of an integral membrane receptor protein
Endocytosis – Phagocytosis and Lysosomes
Pinocytosis
ReceptorMediated
Endocytosis
Transmembrane Transport of
Nonpolar vs. Polar Substances
• Nonpolar substances cross a membrane through the
phospholipid bilayer
– ineffective barrier against the movement of nonpolar
molecules across a membrane
• it is impossible to control the movement of nonpolar
molecules through a membrane
• Polar substances cross a membrane by moving through
integral membrane transporting proteins
– Carriers
– Pumps
– Channels
– Each carrier, pump and channel has a unique tertiary
shape and therefore is designed to transport different
substances across a membrane
• the cell can control the movement of polar molecules
through a membrane by controlling the activity of the
transporting proteins
Carriers and Pumps
• Integral membrane proteins that “carry” large polar
molecules (monosaccharides, amino acids, nucleotides…)
by changing their shape between 2 conformations
– “flip-flop” between being open to the ECF and ICF
– transport substances much more slowly across a
membrane compared to channels
• the maximum rate at which these proteins can
transport substances across a membrane is limited by
how fast they can change shapes
• Pumps hydrolyze a molecule of ATP and use the energy to
transport substances across the membrane
• The movement of only one substance across a membrane is
called uniport
• The movement of more than one substance across a
membrane is called cotransport
Types of Cotransport
• 2 or more substances are simultaneously carried across the
cell membrane by a carrier
• Symport
– 2 substances are moved across a membrane in the same
direction
• Antiport
– 2 substances are moved across a membrane in opposite
directions
Channels
• Integral membrane proteins containing a water filled hole
(pore) which allows the movement of small polar
substances (ions and water)
– transport substances very quickly across membrane
• there is virtually no limit to the rate at which
substances can cross the membrane through channels
– some channels have “gates” which can be:
• open
– allows ion to cross the membrane
• closed
– does not allow ion to cross the membrane
Transmembrane Transport
• Active
– a transport process that uses an energy source produced
by the cell for the movement of a polar substance
through a membrane
– substance(s) moves UP a concentration gradient
– uses pumps for primary active transport
– uses carriers for secondary active transport
• Passive
– a transport process that DOES NOT use an energy
source produced by the cell for the movement through a
membrane
– substance(s) moves DOWN a concentration gradient
• Diffusion
– uses channels or carriers to transport polar substances
through a membrane
Concentration Gradients
• The difference in the amount of a substance between 2
locations
– region of greater amount vs. region of lesser amount
– the difference may be LARGE or very small
– may exist across a physical barrier (membrane)
– may exist across a distance without a barrier
• Form of mechanical energy
– location of greater amount provides more collisions
– collisions cause substances to move away from one
another
• net movement from location of greater amount to
locations of lesser amounts
Concentration Gradients
Concentration Gradients and
Transmembrane Transport
• The movement of a substance from a region of lesser
amount to a region of greater amount:
– is an “uphill” movement
– requires an energy source
• Active Transport
– causes the gradient to increase
• The movement of a substance from a region of greater
amount to a region of lesser amount:
– is a “downhill” movement
– releases energy during transport
• Passive Transport
– causes the gradient to decrease
Transmembrane Concentration Gradients and
Equilibrium
• Equilibrium
– a condition that is met when substances move down a
gradient until there is NO gradient
• equal concentrations of a substance between 2
locations
• no net movement of substances from one location to
another
– substances do continue to move due to heat energy
– Equilibrium of substances across the various membranes
in the cells of the body = DEATH
• your body is in a constant battle to ensure equilibrium
of solutes across the membranes is never reached
Transmembrane Concentration Gradients and Steady
State
• Steady State
– a condition where a gradient is PRESENT and is
MAINTAINED by the constant expenditure of energy
by the cell
– unequal concentrations of a substance between 2
locations
– no net movement of substances from one location to
another
• one substance moving passively down the gradient, is
exactly balanced by one substance moving actively
up the gradient
– Life depends upon the ability of the organism to exist in a
steady state
Passive Transmembrane Transport – Diffusion
• Movement a substance to move DOWN its gradient
• Releases energy as a result of the movement
• Does not occur if there is no gradient
– Equilibrium
• Nonpolar molecules diffuse through the nonpolar
phospholipid bilayer in a process called simple diffusion
• Polar molecules require the help (facilitation) of integral
membrane proteins (channels or carriers) to cross the
bilayer in a process called facilitated diffusion
Facilitated Diffusion through a Carrier
Factors Affecting the Rate of Diffusion
• The rate at which a substance moves by way of diffusion is
influenced by 3 main factors
– Concentration gradient
• a large concentration gradient, results in a high rate of
diffusion
– Temperature
• a high temperature, results in a high rate of diffusion
– heat causes motion
– Size of the substance
• a large substance, has a low rate of diffusion
– larger objects move more slowly
Osmosis
• The diffusion of water (solvent) across a selectively
permeable membrane
– requires “water channels” called aquaporins
• Water diffuses toward the location with the greatest amount
of solutes (region of less water)
• Solutes generate a force that “pulls” water molecules
causing them to move toward the solutes
– osmotic pressure
• the greater the osmotic pressure, the greater the
amount of water movement
• Water in a container (such as a cell) exerts a pressure on the
walls of the container
– hydrostatic pressure
• the greater the amount of water in a container, the
greater the hydrostatic pressure
• Osmotic pressure is the amount
of pressure which must be applied
to the membrane in order to oppose
osmosis.
 due to the force generated by
solutes which attracts water
molecules towards them.
Tonicity
• The ability of the solutes in the ECF to cause osmosis across
the plasma membrane
• Isotonic (same)
– solute concentration in ECF = ICF
– water does not move into or out of cell causing no
change in the cell volume
• no change in intracellular hydrostatic pressure
• Hypertonic (more than)
– solute concentration in ECF > ICF
– water diffuses out of the cell causing the cell to shrink
(crenate)
• intracellular hydrostatic pressure decreases
• Hypotonic (less than)
– solute concentration in ECF < ICF
– water diffuses into the cell causing the cell to swell
• intracellular hydrostatic pressure increases
Cell in a Hypotonic Solution.
• Cell swells
• Increases hydrostatic pressure
Osmosis and cell volume changes
Primary Active Transport
• Integral membrane pumps use the energy stored in a
molecule of ATP to transport substances across a
membrane UP a concentration gradient
– The pump:
• hydrolyzes the high energy bond in a molecule of ATP
(releasing energy)
• uses the energy of ATP hydrolysis to “flip-flop”
between conformations while moving substances UP a
concentration gradient
• This process converts chemical energy (ATP) to mechanical
energy (gradient across the membrane)
– the gradient can be used if necessary by the cell as a form
of energy to do work
Examples of Primary Active Transport
• Na+,K+-ATPase (Na+,K+ pump)
– located in the plasma membrane
– actively cotransports:
• 3 Na+ from the ICF (lesser amount) to the ECF
(greater amount)
• 2 K+ from the ECF (lesser amount) to the ICF (greater
amount)
– creates/maintains a Na+ gradient across the cell
membrane
– creates/maintains a K+ gradient across the cell membrane
Sodium, Potassium ATPase
Secondary Active Transport
• Integral membrane carriers move at least 2 different
substances across a membrane
– One substance moves across a membrane UP a
concentration gradient
– One substance moves across a membrane DOWN a
concentration gradient
– The movements of the substance DOWN a concentration
gradient releases energy which the carrier uses to “flipflop” between conformations and move a second
substance UP a concentration gradient
• “piggyback” transport
• This type of transport is called secondary because this
process is driven by a gradient that is created by a previous
occurring primary active transport process
Example of Secondary Active Transport
• Na+, glucose cotransporter
– located in the plasma membrane
– cotransports:
• Na+ DOWN its concentration gradient
– from the ECF (greater amount) into the ICF (lesser
amount)
• gradient created by the Na+,K+-ATPase
– releasing energy that is used by the cotransporter to
transport:
• glucose UP its concentration gradient
– from the ECF (lesser amount) into the ICF (greater
amount)
Example of Secondary Active Transport
• Na+, glucose cotransporter
– located in the plasma membrane
– cotransports:
• glucose UP its concentration gradient from the ECF
into the ICF driven by the energy released from the
movement of:
• Na+ DOWN its concentration gradient (created by the
Na+,K+-ATPase) from the ECF into the ICF
Na+, Glucose Cotransporter
Na+, Glucose Cotransporter
Membrane Potential
• Although the total solute concentration in the ICF and ECF
are equal, there is an uneven distribution of charged
substances across the cell membrane of every cell in the
body
– creates an electrical potential (energy) between the ICF
and ECF
– measured as a voltage
• in millivolts (mV)
– causes the cell membrane to be polarized
• a measurable charge difference between the ICF and
ECF
• The ICF is negatively charged compared to the ECF
– a typical membrane potential is –70 mV
• In an UNSTIMULATED (resting) cell this potential
remains constant and is referred to as the resting membrane
potential (RMP)
Resting Membrane Potential
Basis of the Resting Membrane Potential
• Due to the permeability characteristics of the plasma
membrane to charged (polar) substances
– permeability is the ease in which one substance can move
through another substance
• Permeable charged substances
– K+
– Na+
Basis of the Resting Membrane Potential
• In a resting cell, Na+ and K+ are constantly pumped across
the cell membrane by the Na+,K+-ATPase maintaining:
– a high Na+ concentration in the ECF
– a low Na+ concentration in the ICF
– a high K+ concentration in the ICF
– a low K+ concentration in the ECF
Basis of the Resting Membrane Potential
Diffusion of Na+ and K+
• There is a constant diffusion of Na+ into the cell by:
• Na+ channels that are always open (leaky)
• There is a constant diffusion of K+ out of the cell by:
• open K+ channels that are always open (leaky)
• The permeability of the cell membrane in a resting cell to
potassium is approximately 40 times greater than the
permeability to sodium
– due to a much larger number of potassium leak channels
compared to sodium leak channels
• When a cell is at rest, the pumping of the Na+,K+-ATPase,
exactly equals the diffusion of Na+ and K+
– results in a steady state condition
Contribution of Na+ to the RMP
• If the cell membrane were permeable only to sodium then
sodium would diffuse into the cell
– as sodium diffuses into the cell it causes the inside of the
cell to become positively charged (it only takes a few
ions because each ion has a large charge) which begins to
reduce additional sodium ion entry (due to repulsion)
• Sodium diffusion stops when the inside of the cell has 58
more mV of charge compared to outside (membrane
potential = +58 mV)
– at this potential, the concentration gradient moving Na+
into the cell exactly balances the positive electric charge
repelling Na+ out of the cell
– Equilibrium potential for Na+ (ENa)
Contribution of K+ to the RMP
• If the cell membrane were permeable only to potassium then
potassium would diffuse out of the cell
– as potassium diffuses out of the cell it causes the inside
of the cell to become negatively charged (it only takes a
few ions because each ion has a large charge) which
begins to reduce additional potassium ion exit (due to
attraction)
• Potassium diffusion stops when the inside of the cell has 90
less mV of charge compared to outside (membrane potential
= -90 mV)
– at this potential, the concentration gradient moving K+
out of the cell exactly balances the negative electric
charge attracting K+ into the cell
– Equilibrium potential for K+ (EK)
RMP
• Note that the RMP is neither equal to ENa or EK, but is
somewhere between these 2 values
• If the permeability of these 2 ions through the cell
membrane were exactly the same, the RMP would be
exactly between the values of ENa and EK, or -16 mV.
• However, the permeability of the cell membrane to
potassium is approximately 40 times greater than that of
sodium due to a much greater number of potassium leak
channels.
• This causes potassium to have a much greater influence on
the RMP compared to sodium, which is why at -70 mV the
RMP is closer to -90 mV than +58 mV.