Physio 1, Fall ’08, LPC

Chapter 5 – Membrane Dynamics

I - Mass Balance & Homeostasis

A. Mass Balance

Total amount (or load) of substance x in body = intake + production - excretion – metabolism  (-> homeostasis)

Clearance

Mass flow (amount x/min) = concentration (amount x/vol) X volume flow (vol/min)

Ex: 50 g glucose/1000 mL X 2mL solution/min = 100(g)(mL)/1000(mL)(min) = 0.1 g glucose/min

B. Homeostasis in Body – dynamic steady state

Osmotic equilibrium = amount of solute/volume same in extracellular & intracellular compartments

Chemical disequilibrium – major solutes different in two body compartments. Requires energy to maintain.

Electrical disequilibrium – inside of cell negative compared to extracellular fluid

II – Diffusion

A. General properties  

Passive
Table 5-1     

Cell membranes are selectively permeable. Depends on size of molecule and its lipid solubility.

Ions do not move by diffusion.

B. Lipophilic Molecules
Diffusion across phospholipid bilayer according to Fick’s law:

                                    (Surface area)(Conc. Gradient)(Membrane permeability)
Rate of Diffusion =                                 Membrane Thickness

III – Protein Mediated Transport

A. Proteins - Structural, Enzymes, Receptors, Transporters

B. Transporters 

Open channels usually open

Water channels, ion channels
Selectivity depends upon size of channel & charge of proteins

Gated channels - have gate that can be controlled

respond to chemical, mechanical, or electrical signals

C. Carrier Proteins – bind specific substrates & move across membrane by changing shape

Uniport, symport, antiport

Facilitated diffusion -> equilibrium on both sides of membrane

Can -> net import if product is used or stored in another form

Active transport

moves substances against concentration gradient
uses energy
substrate binds to membrane carrier, carrier changes conformation, releases substrate on other side of membrane

Primary Active Transport

Energy comes directly from ATP via ATPase
Ex: Na+ -K+ -ATPase – pumps 3 Na+ out of cell/2 K+ into cell/ATP

1. 3 Na+ from ICF bond to carrier
2. ATPase phosphorylated by ATP, binds to carrier protein
3. 3 Na+ released into ECF
4. 2 K+ from ECF bind to carrier
5. Pi released & carrier changes conformation
6. 2 K+ released to ICF

Secondary Active Transport

Energy comes from one molecule moving down its concentration gradient to push other molecule again its concentration gradient

Both molecules same direction = symport
Molecules move in opposite direction = antiport

Ex: Na+ -glucose (SGLT) (symport)

1. Na+ from outside cell binds to carrier, -> glucose binding site
2. Glucose binds to carrier
3. Carrier conformation changes, -> opening towards inside cell
4. Na+ & glucose released into cell

Summary

Energy from metabolism -> ATP

Primary active transport

OR

Secondary active transport

Carrier–mediated transport:

Specific – moves only one molecule or group
Competitive – similar molecules or groups can bind (although with a lower affinity) and block carrier
Will saturate – can be more substrate than unoccupied carrier molecules

IV – Vesicular Transport

Phagocytosis – cell membrane protrudes, surrounds particle, forms vesicle, brings vesicle inside cell, vesicle combines with lysosome, vesicle contents digested. Requires energy.

Endocytosis – cell membrane indents, surrounds molecule, forms vesicle, brings vesicle inside cell, releases contents inside cell. Requires energy.

Pinocytosis – non-selective
Receptor–mediated – Highly selective. Ligand binds to membrane receptor.

Exocytosis – vesicle fuses with cell membrane, releases molecule outside cell. Requires Energy.

V – Transepithelial Transport

Moves molecules through membranes on both sides of epithelia
Apical (mucosal) membrane faces lumen of organ
Basolateral (serosal) membrane faces ECF
Cells polarized, ie, different activities on apical & basolateral sides
Epithelial cells bound tightly together
Transport into ECF = absorption. Transport into lumen = secretion.

Example: glucose transport from intestine into ECF

1. Secondary active transport brings glucose and Na+ from lumen into cell
2. Na+ into ECF by primary active transport
3. Glucose into ECF by facilitated diffusion

VI – Osmosis & Tonicity

Osmosis = movement of water to area of its lower concentration

osmotic pressure – pressure needed to offset force of osmosis

Osmolarity = number of particles/liter

expressed in osmoles/L or OsM
OsM = molarity X number of particles/molecule

Ex: Table 5-6

Tonicity – depends on concentration of solutions and solute and solvent permeabilities

Penetrating solute can cross cell membrane
Nonpenetrating solutes cannot cross cell membrane

Hypotonic, isotonic, hypertonic 

Predict tonicity:

1. Cell with higher concentration of nonpenetrating solutes than solution -> cell swells
2. Cell with lower concentration of nonpenetrating solutes than solution -> cell shrinks
3. Concentration of nonpenetrating solutes same in cell and solution -> no net movement of H2O

Learn Table 5-8

VII – Resting Membrane Potential

Electricity Review

1. Amount of electrical charge produced in any process = 0
2. Opposite charges attract each other, likes repel
3. Separating negative from positive charges requires energy
4. Electrons flow through a conductor, do not through an insulator

Cell membrane allows separation of electrical charge

Ex: Fig  5-32 - note physiological measurements = inside cell (negative) relative to zero outside cell

Electrical gradient between extracellular fluid & intracellular fluid = resting membrane potential difference = membrane potential = Vm

Chemical disequilibrium also, -> electrochemical gradient

Resting Membrane Potential
1. K+ leaks out of cell (inside cell becomes negative)
2. Na+ attracted into cell (because of electrical gradient) but cell relatively impermeable to Na+
3. Na+ -K+ -APTase pumps 3 Na+ out of cell/2 K+ pumped in, contributes to membrane potential, electrogenic pump

Changes in Ion Permeability Change the Membrane Potential

Permeability change -> change in potential
Takes very few ions to -> big change in membrane potential

Depolarization = decrease in Vm  (more positive) (entry into cell or retention of positive ions)
Repolarization – resting Vm restored
Hyperpolarization = increase in Vm (more negative) (entry of negative ions into cell)

VIII – Insulin Secretion – example of integrated membrane processes

Beta cell at rest

1. low blood glucose -> lower ATP production in beta cell
2. KATP channels open and K+ leaks out of cell, cell at resting membrane potential
3. Voltage-gated Ca++ channel closed
4. No insulin vesicles released

Beta cell secreting insulin

1. high blood glucose -> increased ATP
2. KATP channels close
3. Cell depolarizes and Ca channels open
4. Ca++ entry acts as an intracellular signal
5. Signal triggers exocytosis of insulin