U N I T II

Textbook of Medical Physiology, 11th Edition

Chapter 4:
Transport of Substances Through
the Cell Membrane

GUYTON & HALL

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 Lipid Bilayer:
• barrier to water and water-soluble substances

CO2
N2 O2
ions glucose H2O
urea halothane

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 Permeability coefficients (cm/sec)
(** across an artificial lipid bilayer)

water 10-2 high permeability

urea
10-4
glycerol
10-6
glucose
10-8

Cl- 10-10
K+
Na+ 10-12 low permeability

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 Molecular Gradients
inside outside
(in mM) (in mM)

Na+ 14 142
K+ 140 4
Mg2+ 0.5 1-2
Ca2+ 10-4 1-2
H+ (pH 7.2) (pH 7.4)
HCO3- 10 28
Cl- 5-15 110
SO42- 2 1
PO3- 75 4

protein 40 5
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 Proteins:
• provide “specificity” to a
membrane
• provide “function”
ion channels carrier proteins

K+

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 Diffusion Active Transport
• occurs down a concn. • occurs against a concn.
gradient gradient
• no mediator or involves • involves a “carrier”
a “channel” or “carrier”
• no additional energy • requires ENERGY

Figure 4-2; Guyton & Hall

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 Simple Diffusion
(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)

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 Ion Channels

Characteristics:
ungated
• determined by size, shape, distribution of charge, etc.
gated
• voltage (e.g. voltage-dependent Na+ channels)
• chemically (e.g. nicotinic ACh receptor channels)

in

out
Na+ and other
Na+ ions
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 How to Study?

• “Patch Clamp”
• Nobel Prize in
Physiology & Medicine
-1991
Extracellular

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Inside Cell
 Ion Channels

in

out
Na+

Figure 4-5; Guyton & Hall

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 Simple vs. Facilitated
simple diffusion
rate of diffusion  (Co-Ci)
rate of
diffusion

Vmax
Tm facilitated diffusion

Concn of substance

What limits maximum rate of

facilitated diffusion?
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 Facilitated Diffusion
(also called carrier mediated diffusion)

Rate of diffusion is limited by

− Vmax of the carrier
protein
− the density of carrier
proteins in the membrane
(i.e., number per unit area)

Figure 4-7; Guyton & Hall

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 Factors that affect
the net rate of diffusion:

1. Concentration difference (Co-Ci)

net diffusion  D (Co-Ci)

Figure 4-8; Guyton & Hall

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 Net Diffusion

A B

Can a molecule diffuse from side B to

side A?
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 2. Electrical potential (EMF)


    
  

     
    
     When will the
      
negatively charged

     molecules stop
   entering the cell?
   

The Nernst potential (equilibrium potential) is the theoretical
intracellular electrical potential that would be equal in magnitude but
opposite in direction to the concentration force.

EMF (mV) = ±61 log (Co / Ci)

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 3. Pressure difference

• Higher pressure results in increased energy available to

cause net movement from high to low pressure.

Figure 4-8; Guyton & Hall

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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.

Figure 4-9; Guyton & Hall

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 Osmotic Pressure:
the amount of pressure required to counter osmosis

Osmotic pressure is
attributed to the
osmolarity
of a soln

Figure 4-10;
Guyton & Hall
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 Major determinant of osmotic pressure

 

100 g 1000 g
in 1 L in 1L

Solute A Solute B
Mw = 100 Mw = 1000

Which solution has the greatest osmolarity?

Which has the greatest molar concn?
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 concn

or mOsm/L of particles per liter soln

mM (millimolar) = index of concn of

or mM/L molecules per liter soln

150 mM NaCl = 300 mOsm

300 mM glucose = 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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 Isotonic and Isosmotic

Isotonic Isosmotic
150 mM NaCl Yes Yes
300 mOsm NaCl Yes Yes
0.9% NaCl Yes Yes
300 mM glucose Yes Yes
300 mOsm glucose Yes Yes
5% glucose Yes Yes
300 mM urea No Yes
300 mOsm urea No Yes

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 Steady-state cell volume
is dependent upon the concentration of impermeant particles
in the extracellular fluid (e.g. Na+, K +, protein-)

Permeant particles cause only transient changes in cell

volume (e.g. urea, glycerol)

Time course of the change in cell volume is dependent on

the permeability of the particle

higher permeability = more transient the change

urea > glycerol
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 Example:

Swell
300 mOsm Shrink
NaCl
Time course??
200 mOsm glycerol
200 mOsm NaCl

Shrink then swell

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 Example:

Swell
300 mOsm Shrink
NaCl
No change??
200 mOsm
Urea

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 Clinical Abnormalities
of Fluid Volume Regulation

Hypernatremia (increased plasma Na):

• increased water loss
• excessive sweat loss
• central or nephrogenic diabetes insipidus
**decreased ADH secretion or responsiveness to ADH

Hyponatremia (decreased plasma Na):

• large water ingestion
• Syndrome of Inappropriate ADH Secretion (SIADH)
**too much ADH leads to water retention, hyponatremia,
and excretion of concentrated urine.
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 Active Transport

Primary Active Transport

• molecules are “pumped” against a concentration
gradient at the expense of energy (ATP)
– direct use of energy

Secondary Active Transport

• transport is driven by the energy stored in the
concentration gradient of another molecule (Na+)
– indirect use of energy

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 Primary Active Transport

1. Na+/K+ ATPase
• carrier protein located on the plasma membrane of
all cells

• plays an important role in regulating osmotic balance

by maintaining Na+ and K+ balance (inhibition by
ouabain causes cells to swell and burst!)

• requires one to two thirds of cells energy!

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  subunit
• 100,000 MW
• binds ATP, 3 Na+, and 2 K+

 subunit
• 55,000 MW
• function ???

Figure 4-11; Guyton & Hall

Transport is electrogenic but contributes

less than 10% to the membrane potential

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 2. Ca2+ ATPase
• present on the cell membrane and the sarcoplasmic
reticulum
• maintains a low cytosolic Ca2+ concentration

3. H+ ATPase
• found in parietal cells of gastric glands (HCl secretion)
and intercalated cells of renal tubules (controls blood
pH)
• concentrates H+ ions up to 1 million-fold

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 Saturation
• similar to facilitated diffusion
• rate limited by Vmax of the transporters

Energetics
• up to 90% of cell energy expended for active
transport!

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 Secondary Active Transport
- co-transport and counter-transport -

1. Co-transport (co-porters): substance is

transported in the same direction as the “driver”
ion (Na+)
Examples:
outside
Na+ AA Na+ gluc Na+ 2 HCO3-

inside
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 2. Counter-transport (anti-porters): substance is
transported in the opposite direction as the “driver” ion
(Na+)

Examples:
outside
Na+ Na+ Na+/HCO3-

Ca2+ H+ Cl-/H+

inside
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 Q: How do cardiac glycosides
increase cardiac contractility?

Glycosides (eg. digoxin) inhibit the Na/K ATPase…

• increase intracellular Na+
• decrease Na+ gradient
• decrease Na+/Ca2+ counter-transport
• increase intracellular Ca2+

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 Q: How do cardiac glycosides
increase cardiac contractility?

Na+ Na+
K+

Digoxin has been a

Na+ cornerstone for the treatment
of heart failure for decades
Ca++ and is the only oral inotropic
support agent currently used
in clinical practice.

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 Transcellular Transport of Glucose / AA

extracellular
lumen epithelium fluid
low high low

AA AA AA
Na+
Na+
K+

glucose glucose glucose

Na+
Na+
K+

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