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Intracellular vs. extracellular concentrations. Note: Na + , K + , Cl - , phosphate, - & protein -. [IC] vs. [EC] important points. *Intracellular cations = Intracellular anions (mEq/L) *Extracelluar cations = Extracellular anions (mEq/L) *miniscule, unmeasurable differences

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intracellular vs extracellular concentrations
Intracellular vs. extracellular concentrations

Note:

Na+, K+, Cl-,

phosphate,- & protein-

ic vs ec important points
[IC] vs. [EC] important points

*Intracellular cations = Intracellular anions (mEq/L)

*Extracelluar cations = Extracellular anions (mEq/L)

*miniscule, unmeasurable differences

Intracellular particles = Extracellular particles

i.e. IC osmolality = EC osmolality

membrane transport overview
Membrane transport overview

No carrier:

simple diffusion (lipid soluble substances)

diffusion through ion channels

diffusion through water channels

Carrier mediated transport

facilitated diffusion (passive)

primary active transport (active, uses ATP)

secondary active transport (active, uses ion gradient)

Endocytosis & exocytosis

simple diffusion
Simple diffusion

Through phospholipid bilayer

Lipid soluble substances

e.g. O2, CO2, NH3, N2, fatty acids, steroids, ethanol,

Passive (down concentration gradient)

No carrier ( no saturation, competition)

simple diffusion flux
Simple diffusion (flux)

fig 4-3

At equilibrium:

compartment 1 concentration = compartment 2 concentration

one-way flux (left  right) = one-way flux (right  left)

net flux = 0

simple diffusion graph of c i vs time
Simple diffusion (graph of Ci vs. time)

fig 4-4

Graph shows that transport is passive

i.e. over time Ci will reach, but never exceed Co

simple diffusion graph of rate vs concentration
Simple diffusion (graph of rate vs. concentration)

Graph shows that transport is not carrier mediated;

because no saturation of transport rate

properties of ion channels
Properties of ion channels

Usually (not always) highly specific for the ion

Ion transport is passive

ions are charged

therefore, gradient depends on concentration & charge

combination is “electrochemical gradient”

Channels open and close spontaneously

Percentage of “open time” can be regulated (gating)

Open time regulated by:

binding of ligands to the channels (ligand gating)

voltage difference across membrane (voltage gating)

stretch of membrane (mechanical gating)

covalent alteration of channel protein

facilitated diffusion properties
Facilitated diffusion (properties)

Passive, carrier mediated

Examples: glucose into most cells (not luminal membrane of kidney or intestine), urea, some amino acids

Kinetics:

shows: passive

shows: carrier mediated

primary active transport na k atpase pump
Primary active transport (Na+/K+ ATPase pump)

3 Na+’s out, 2 K+’s in, 1 ATP hydrolyzed

fig 4-11

primary active transport properties
Primary active transport properties

Active (energy from direct hydrolysis of ATP)

Carrier mediated

Used when:

many ions moved (e.g. 5 for Na+/K+ ATPase pump)

ions moved against steep gradient (Ca++ ATPase in muscle, H+/K+ ATPase in stomach, H+ ATPase in kidney)

primary active transport kinetics
Primary active transport kinetics

shows active transport

shows carrier mediated

secondary active transport properties
Secondary active transport properties

Active (energy from ion gradient, usually Na+)

Carrier mediated

Can be cotransport (symport) or countertransport (antiport)

Examples (many):

Na+/amino acids, Na+/glucose (luminal membrane kidney, GI tract), *Na+/H+ kidney, *Ca++/3Na+ muscle,

*Cl-/HCO3- red cell. (* = countertransport)

Kinetics

see primary active transport graphs

water transport aka osmosis
Water transport (aka osmosis)

Water moves through aquaporin channels

Water moves passively down its own concentration gradient

Dissolving solute in water reduces the water concentration

Water therefore moves from a dilute solution to a more concentrated solution

The “solute concentration” depends on the number of particles

The number of particles is called “osmolarity” (?osmolality?)

The units of osmolarity are milliosmoles/L (mOsm/L)

calculation of osmolarity
Calculation of osmolarity
  • The osmolarity of a 100 mM glucose solution is 100 mOsm/L
  • A 100 mM NaCl solution dissociates into 100 mM Na+ and 100 mM Cl-; its osmolarity is therefore 200 mOsm/L
  • Assuming complete dissociation, calculate the osmolarity of the following solutions:
  • 100 mM NaCl, 50 mM urea
  • 2. 200 mM glucose, 30 mM CaCl2

Answer: 250 mOsm/L

Answer: 290 mOsm/L

red cells in solution
Red cells in solution

Notes: nonpenetrating solutes, cell osmolarity ~300 mOsm/L

fig 4-19

osmolarity and tonicity
Osmolarity and tonicity

Osmolarity is a measure of the total number of particles

Tonicity is a measure of the solute particles which do not cross the cell membrane “non-penetrating solutes”

Tonicity therefore depends on the properties of the solute and the cell membrane

For example, urea crosses most cell membranes, and will enter the cell down its concentration gradient

A solution of 300 mM urea is isosmotic to red cells but is hypotonic

osmolarity and tonicity problems
Osmolarity and tonicity problems
  • Consider a solution of 100 mM NaCl and 200 mM urea. How does its osmolarity and tonicity compare with red cells having an osmolarity of 300 mOsm/L?
  • Answer: hyperosmolar and hypotonic
  • 2. Consider a solution of 125 mM NaCl and 50 mM urea. How does its osmolarity and tonicity compare with red cells having an osmolarity of 300 mOsm/L?
  • Answer: isosmolar and hypotonic
osmolarity important concept
Osmolarity (important concept)

Because cells contain abundant aquaporin channels, water rapidly equilibrates across the cell membrane

Therefore, the osmolarity of virtually all body cells is equal, and equal to the osmolality of extracellular fluid

endocytosis and exocytosis properties
Endocytosis and exocytosis properties

Endocytosis:

pinocytosis, phagocytosis

specificity conferred by receptor mediated endocytosis

route: see next slide

Exocytosis:

release of neurotransmitters, hormones, digestive enzymes

route: rough er  Golgi  secretory vesicles

release usually triggered by  cytosolic [Ca++]

insertion of glucose transporters (insulin),

insertion of water channels (ADH)