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Membrane transport- L1
Faisal I. Mohammed, MD, PhD
Resource: Guyton’s Textbook of Medical Physiology 12th edition.
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Objectives
List trans-membrane transport mechanisms (passive and active)
Describe passive mechanisms (simple diffusion, facilitated diffusion, osmosis, bulk flow)
Describe active mechanisms (primary and secondary active transport mechanisms)
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Major Topics Fluid mosaic model How molecules move across cell membranes
Membrane permeability Molecular gradients Transport mechanisms Ions channels
Equilibrium potential Osmosis and osmotic pressure Tonicity and osmolarity
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A Generalized Cell
1. Plasma membrane
- forms the cell’s outer boundary
- separates the cell’s internal environment from the outside environment
- is a selective barrier
- plays a role in cellular communication
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Structure of the Plasma Membrane
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• barrier to water and water-soluble substances
ions glucose H2Ourea
Lipid Bilayer:
CO2O2N2
halothane
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Plasma Membrane
Flexible yet sturdy barrier The fluid mosaic model - the arrangement of
molecules within the membrane resembles a sea of lipids containing many types of proteins
The lipids act as a barrier to certain substances The proteins act as “gatekeepers” to certain
molecules and ions
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Structure of a Membrane Consists of a lipid bilayer - made up of
phospholipids, cholesterol and glycolipids Integral proteins - extend into or through the
lipid bilayer Transmembrane proteins - most integral
proteins, span the entire lipid bilayer Peripheral proteins - attached to the inner or
outer surface of the membrane, do not extend through it
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Functions of Membrane Proteins
Some integral proteins are ion channels Transporters - selectively move substances
through the membrane Receptors - for cellular recognition; a ligand is
a molecule that binds with a receptor Enzymes - catalyze chemical reactions Others act as cell-identity markers
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Cell Membrane
ionsglucose
H2Ourea
… but, other molecules still get across!
CO2O2N2
halothane
Permeability coefficients (cm/sec)
10-2
10-4
10-8
10-10
10-12
water
ureaglycerol
glucose
Cl-
K+
Na+
10-6
high permeability
low permeability
(** across an artificial lipid bilayer)
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Membrane Permeability
The cell is either permeable or impermeable to certain substances
The lipid bilayer is permeable to oxygen, carbon dioxide, water and steroids, but impermeable to glucose
Transmembrane proteins act as channels and transporters to assist the entrance of certain substances, for example, glucose and ions
Molecular Gradients
Na+
K+
Mg2+
Ca2+
H+
HCO3-
Cl-
SO42-
PO3-
protein
inside(in mM)
141400.510-7
(pH 7.2)10
5-152
75
40
outside(in mM)
14241-21-2(pH 7.4)2811014
5
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• provide “specificity” to a membrane• provide “function”
K+
ion channels carrier proteins
Proteins:
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Diffusion Active Transport
• occurs down a concn. gradient• no mediator or involves a “channel” or “carrier”• no additional energy
• occurs against a concn. gradient• involves a “carrier”
• requires ENERGY
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Passive vs. Active Processes Passive processes – ( downhill) substances
move across cell membranes without the input of any energy; use the kinetic energy of individual molecules or ions
Active processes – (uphill) a cell uses energy, primarily from the breakdown of ATP, to move a substance across the membrane, i.e., against a concentration gradient
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(a) lipid-soluble molecules move readily across the membrane(rate depends on lipid solubility)
(b) water-soluble molecules cross via channels or pores
(a) (b)
Simple Diffusion
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ungated• determined by size, shape, distribution of charge, etc.
Characteristics:
Na+
in
outNa+ and other ions
gated• voltage (e.g. voltage-dependent Na+ channels)• chemically (e.g. nicotinic ACh receptor channels)
Ion Channels
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Ion Channels
Na+
in
out
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Diffusion is the most important means water, gases, waste products, and solute transfer across the endothelium
Exchange of gases, substances, and waste products between the capillaries and the tissue cells
Quantity of substance
moved/time
Diffusion coefficient
CSA
Concentration gradient
Capillary permeability
Capillary surface area
Concentrations (in and out)
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Diffusion Across a Membrane
Fick’s Law of Diffusion:
J= net rate of diffusion in moles or grams per unit timeD= diffusion coefficient of the diffusing solute in the
membrane which is proportional to where S= lipid solubilty, Mwt= molecular weight.
A= area of the membraneC= concentration difference across the membraneX= thickness of the membrane
X
CDAJ
./ MwtS
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Diffusion of lipid-insoluble molecules is restricted to the pores
Movement of solutes across endothelium is complex and involves: Attractions between solute and solvent Interactions between solute molecules Pore configuration Molecular charge > 60,000 MW do not penetrate the endothelium < 60,000 MW penetrate at a rate inversely
proportional to their size
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Lipid-soluble molecules pass directly through the lipid membranes of the endothelium and the pores
Solubility (oil-to-water partition coefficient) provides good index of ease of transfer through endothelium
O2 and CO2 readily pass through endothelium Hb is only 80% saturated entering the
capillaries (diffusion from arterioles) CO2 loading shifts the oxyhemoglobin
dissociation curve in the pre-capillary vessels (countercurrent exchange)
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Simple Diffusion, Channel-mediated Facilitated Diffusion, and Carrier-mediated Facilitated Diffusion
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Channel-mediated Facilitated Diffusion of Potassium ions through a Gated K + Channel
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Glucosetransporter
Glucosegradient
Glucose
Extracellular fluid Plasma membrane Cytosol
1
Glucosetransporter
Glucosegradient
Glucose
Extracellular fluid Plasma membrane Cytosol
1
2
Glucosetransporter
Glucosegradient
Glucose
Glucose
Extracellular fluid Plasma membrane Cytosol
1
2
3
Carrier-mediated Facilitated Diffusion of Glucose across a Plasma Membrane
rate of diffusion
Concen of substance
simple diffusion
Simple vs. Facilitated
facilitated diffusion
What limits maximum rate of facilitated diffusion?
Tmax (Vmax)
rate of diffusion (Co-Ci)
Km
½ Tmax
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Rate of diffusion is limited by − Tmax Transport maximum (Vmax -velocity maximum) of the carrier protein − the density of carrier proteins in the membrane (i.e., number per unit area)The capacity is determined by Tmax and the affinity is determined by Km
Facilitated Diffusion (also called carrier mediated diffusion)
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Factors that affect the net rate of diffusion:
1. Concentration difference (Co-Ci)net diffusion D (Co-Ci)
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Factors Affecting Diffusion Permeability of the cell membrane Temperature Electrochemical gradient of the substance across the
membrane Lipid solubility of the substance Thickness of the cell membrane Size of the molecules M. Wt Size of the ion Charge of the ion
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A B
Net Diffusion
Can a molecule diffuse from side B to side A?
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3. Pressure difference
• Higher pressure results in increased energy available to cause net movement from high to low pressure.
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Special types of passive transport
Bulk flow- pressure difference Filtration- hydrostatic pressure gradient Osmosis-water movement
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Osmosis:- Net diffusion of water -
Osmosis occurs from pure water toward a water/salt solution. Water moves down its concn gradient.
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Osmosis
Net movement of water through a selectively permeable membrane from an area of high concentration of water (lower concentration of solutes) to one of lower concentration of water
Water can pass through plasma membrane in 2 ways:1. through lipid bilayer by simple diffusion2. through aquaporins, integral membrane proteins
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Tonicity and its effect on RBCS
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Osmotic Pressure:
the amount of pressure required to counter osmosis
Osmotic pressure is attributed to the osmolarityof a solution
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Osmotic Pressure Van’t Hoff’s law
= RT nC
= osmotic pressure mmHg
R = ideal gas constant
T = absolute temperature in kelvins (273+centigrade degrees)
C = concentration of solutes in osmoles per liter
n = number of dissociated ions of the substances
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Osmotic Pressure
Oncotic pressure
Reflection coefficient(relative impediment to passage
through capillary wall)
Gas constant Absolute Temperature
Solute (albumin) concentration in and
out
= Ranges between 1 for none permeable molecules to 0 for freely permeable molecules
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Major determinant of osmotic pressure
Solute AMw = 100
Solute BMw = 1000
100 gin 1 L
1000 gin 1L
Which solution has the greatest osmolarity?Which has the greatest molar concentration?Which has the greatest number of molecules?
(6.02 x 1023 particles)
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Relation between osmolarity and molarity
mOsm (millisomolar) = index of the concentration or mOsm/L of particles per liter solution
mM (millimolar) = index of concentration of or mM/L molecules per liter solution
150 mM NaCl =
300 mM glucose =
300 mOsm
300 mOsm
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Estimating Plasma Osmolarity
Plasma is clinically accessible. Dominated by [Na+] and the associated
anions Under normal conditions, ECF osmolarity
can be roughly estimated as:
POSM = 2 [Na+]p 270-290 mOSM
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