Download Principles of physiologic function

Principles of physiologic function
Cell membrane physiology
NU/Y2 2015
Objectives
• Name different components of cell membrane
• Describe the role of the cell membrane to
maintain cell life
• Explain the role of protein transporter
• List the modes of the transport
• Give examples and apply on a given organ
NU/Y2 2015
OVERVIEW
• All cells are enclosed within a membrane that
separates the inside of the cell from the
outside.
• This barrier allows the cells to create an
internal environment that is optimized to
support the biochemical reactions required for
normal function.
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Differences in cell morphology
Overview
• Most cells also contain an identical set of
membrane-bound organelles:
• nuclei, endoplasmic reticulum (ER), lysosomes,
Golgi apparatuses, mitochondria.
• Specialization of cell and organ function is usually
achieved by adding a novel organelle or structure,
or by altering the mix of membrane proteins that
provide pathways for ions and other solutes to
move across the barrier.
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CELLULAR ENVIRONMENT
• Extracellular fluid (ECF): ions, Glucose, Protein
– The biochemical reactions required of cells can
only occur if free Ca concentrations are lowered
ten-thousand fold
2
• Plasma membrane (Cell): Barrier separate ECF
from ICF (cytosol)
• Intracellular fluid (ICF): sustain life
– More K, free Protein than EC; slightly more acid
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Membrane component
• Membrane component:
– Lipid bilayer: barrier function. O2 CO2 alcohol
(lipophilic)
– cholesterol makes it stronger and more rigid
– Protein: cell communication and transport
hydrophilic molecule
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Membrane Structure
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Membrane Lipid Bilayer
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Cholesterol location in the membrane
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Membrane protein
• Proteins are grouped on the basis whether
they localize to the membrane surface
(peripheral) or are integral to the lipid bilayer.
• Peripheral
– IC: enzyme, regulator, skeleton (spectrin, actin,
ankrin)
– EC: glycophosphatidylinositol (GPI) anchor
proteins: enzyme, A/G, adhesion molecule
• Integral: ion channels transporters receptors
Membrane protein
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Membrane spanning protein
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Diffusion
• Driven force  movement
• Gradient concentration is a driven force for
simple diffusion
• ATP is a chemical force  movement against
gradient = active transport
• Fick law
– The rate at which molecules such as blue dye
cross membranes can be determined using a
simplified version of the Fick law: J = P x A (C1-C2)
Simple diffusion
Diffusion through a lipid bilayer
Protein play a role as
transporter
Charged molecules
• Electrical force (battery + - electrodes) 
movement of charged molecules:
• (+) dye molecules move to negative (-)
electrode.
• When gradient force = electrical force 
electrochemical equilibrium
Charge movement induced by an
electrical gradient
Repellent effect of like charge
Pores, channels, carriers
• Small, nonpolar molecules (e.g., O2 and CO2)
diffuse across membranes rapidly, and they
require no specialized pathway. Most
molecules common to the ICF and ECF are
charged, however, meaning that they require
assistance from a pore, channel, or carrier
protein to pass through the membrane’s lipid
core.
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Transit rate of pore channel carrier
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Pores
• Pores are integral membrane proteins
containing unregulated, water filled passages
that allow ions and other small molecules to
cross the membrane.
• Because AQP is always open, cells must
regulate their water permeability by adding or
removing AQP from the membrane.
Channels
• Ion channels are trans-membrane proteins that
assemble so as to create one or more water-filled
passages across the membrane.
• Channels differ from pores in that the
permeability pathways are revealed transiently
(channel opening) in response to a membranepotential change, neurotransmitter binding, or
other stimulus, thereby allowing small ions (e.g.,
Na, K, Ca2, and Cl) to enter and traverse the lipid
core. They are selectives for each ion
Ion channel opening
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Carriers
• Larger solutes, such as sugars and amino acids,
are typically assisted across the membrane by
carriers.
• Carriers can be considered enzymes that catalyze
movement rather than a biochemical reaction.
• Translocation involves a binding step, which slows
transport rate considerably compared with pores
and channels .
• There are three principal carrier modes:
facilitated diffusion, primary active transport,
and secondary active transport.
Carrier transport for facilitated
diffusion
• Molecule move down its concentration
gradient (high to low) via carrier protein
transport more efficient than simple diffusion
• Carrier can be saturated for a finite number
 Transport maximum: Tm
• Ex: GLUT1 or GLUT4 insulin dependent
Mode of transport by carrier protein
Carrier saturation kinetics
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Primary active transport = pump
• Ion move against its concentration gradient
• Examples
– Na-K ATPase Pump
– H-K ATPase Pump
– Calcium ATPase Pump
Na-K ATPase
• Na-K ATPase: The Na-K ATPase (Na-K
exchanger or Na-K pump) is common to all
cells and uses the energy of a single ATP
molecule to transport three Na out of the cell,
while simultaneously bringing two K back
from the ECF.
Ca2+ ATPases
• Ca2+ ATPases: All cells express a plasma
membrane Ca2+ ATPase (PMCA) that pumps Ca2+
out of the cytoplasm and is primarily responsible
for maintaining intracellular Ca2+ concentrations
at submicromolar levels.
• A related sarco(endo) plasmic reticulum Ca2+
ATPase (SERCA) is expressed in the sarcoplasmic
reticulum of myocytes and the ER of other cells.
SERCA sequesters Ca2+ in intracellular stores.
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H-K ATPase
• H-K ATPase: The H-K ATPase pumps acid and
is responsible for lowering stomach pH, for
example.
• It is also found in the kidney, where it is
involved in pH balance.
Medicine/Physiology
H+-K+ ATPase Pump
Secondary active transport:
• A second class of active transporters use the
energy inherent in the electrochemical
gradient of one solute to drive uphill
movement of a second solute.
• Two transport modes:
– countertransport and
– cotransport.
Countertransport:(antiporters)
• Countertransport: Exchangers (antiporters)
use the electrochemical gradient of one solute
(e.g., Na+) to drive flow of a second (e.g., Ca2+)
in the opposite direction to the first.
• Ex:
– Na-Ca2+ exchanger
– Na+-H+ exchanger and
– Cl--HCO3- exchanger
Cotransport: (symports)
• Cotransport: Cotransporters (symports) use the
electrochemical gradient of one solute to drive
flow of a second or even a third solute in the
same direction as the first
• Ex.
–
–
–
–
–
Na-glucose cotransporter
Na–amino acid cotransporter
Na-Cl cotransporter
K-Cl cotransporter
Na-K-2Cl cotransporter
Na+-Glucose cotransporter
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Na+-K+-2Cl- Cotransporter
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References
• Lippincott’s Illustrated Reviews: Physiology.
Robin R. Preston 2013
• Physiology at a Glance 3rd edition. Jeremy P.T.
Ward 2013
• BRS Physiology 5th edition. Linda S. Costanzo
2011