1. TRANSPORT MECHANISMS LECTURE 8 CHAPTER 6 INTERACTIONS BETWEEN CELLS AND THE EXTRACELLULAR ENVIRONMENT

2. Extracellular environment

3. Body Fluids Intracellular compartment (inside cells) – contains 67% of our water Extracellular compartment (outside cells) contains 33% of our water Of this: a.20% is in blood plasma. b.80% makes up interstitial fluid.

4. A Closer Look at the Extracellular Matrix Ground substance is like a gel composed of glycoproteins and proteoglycans (mostly polysaccharide

5. SOME STUFF PASSES THROUGH, BUT NOT OTHERS AKA “SELECTIVELY PERMEABLE” What can pass through depends on the size of the molecule and its chemical properties Cell membranes are semi-permeable -- Generally not permeable to proteins, nucleic acids, or other large molecules -- Generally permeable to ions, nutrients, and wastes.

6. Categories of Membrane Transport a.Noncarrier-mediated (passive) 1)Simple diffusion of lipid-soluble molecules 2)Simple diffusion of ions through nonspecific channels 3)Simple diffusion of water (osmosis) b.Carrier-mediated 1)Facilitated diffusion (passive) 2)Active transport (active)

7. PASSIVE VERSUS ACTIVE TRANSPORT a.Passive transport: Molecules move from higher to lower concentration without using metabolic energy, with or w/o a membrane. b.Active transport: Molecules move from lower to higher concentration using ATP and specific carrier pumps.

8. Three types of passive transport 1 – simple diffusion – Nonpolar molecules, ions, water, go through the membrane. 2 – facilitated diffusion through a channel protein. E.g. ions, water through aquaporin channels. 3 – facilitated diffusion through a carrier protein e.g. small organic molecules such as glucose.

9. Review of terminology Solvent – liquid into which molecules are dissolved. Solute – molecules that are added to the solvent Solution – solute + solvent Concentration = the amount of solute in a specific amt. of liquid.

10. Net Diffusion means that most of the molecules will move in the direction of lower concentration until an equilibrium state is reached.

11. Fig 6.4 DIFFUSION THROUGH A DIALYSIS MEMBRANE: Proteins (purple) are too big to fit through. Glucose (green) is small enough to fit through, but is at an equil- ibrium, so there is no “net” movement. Small ions and molecules (yellow) can fit through and travel down their concentration gradient

12. Small or nonpolar molecules pass easily. E.g. Oxygen, carbon dioxide, and steroid hormones, water Larger polar molecules cannot pass through the membrane by simple diffusion but need special carrier proteins. E.g. glucose Charged inorganic ions cannot pass through the membrane, but need ion channels. E.g. Na +, K + (see upcoming slide) Review of what can/cannot go through

13. Fig. 6.5: Gas exchange.

14. Ions pass through membrane channels

15. What factors influence the rate of diffusion? a.Magnitude of concentration difference – the driving force for diffusion b.Permeability of the membrane to the molecules c.Temperature of the solution; higher temperature increases the rate d.Surface area of the membrane; increased by microvilli

16. Diffusion of water Aquaporins Water moves toward the side with less water (high solute side) Membrane must be impermeable to solute Solutes that cannot cross and permit osmosis are called osmotically active Osmosis

17. The Effect of Osmosis Water will move into the bag, where there is 360 g/L of sucrose, until an equal concentration of sucrose (270 g/L) is achieved on both sides of the membrane.

18. FIG. 6.9 The force required to stop osmosis is twice as great for a solution of 360 g/L as for a solution of 180 g/L Osmotic pressure – the force required to stop osmosis. -Can be used to describe the osmotic ‘pull’ of a solution. -Pure water has an osmotic pressure of zero

19. There are 6.02 X 10 23 particles in 1 mole. The weight of a mole is the molecular weight of a substance. EXAMPLES: glucose (MW = 180); 1 mole of glucose is 180g NaCl (MW = 58.5); 1 mole of NaCl is 58.5g Sucrose = 342 g ; 1 mole of sucrose is 342 g A 1 Molar solution, 1 M, is the molecular weight of a substance in 1 Liter of water. Moles and Molarity Click here Click here for an intro to moles 1 mole is 6.02 X 10 23 things

20. Molarity vs. Molality “Molarity” – # moles/1 Liter of solution “Molality” – # moles/1 kg of solvent FIG. 6.10 With Molality, we always use the same amount of water (1 kg or 1 L); With Molarity, the amount of water used will differ when used to dissolve solutes of different Molecular weights.

21. Osmolality is the total molality of a solution when you combine all of the molecules within it. EXAMPLE: A 360 g (2 m) glucose solution and a 180 g glucose (1m) + 180 g fructose (1m) solution would have the same osmolality. -These are both 2 Osm solutions. Osmolality

22. NaCl dissociates into Na + and Cl - in water and must be counted as separate particles. NaCl  Na + (aq) + Cl - (aq) A 1m NaCl solution would actually be a 2 Osm solution. Fig. 6.12 – Effect of Ionization on Osmotic Pressure If the membrane is not permeable to glucose, then, water will move by osmosis into the NaCl solution until the osmolality equals 1.5 on both sides of the membrane.

23. Osmolality can be measured by freezing point depression Water freezes at zero degrees Celsius For every osmolal, water freezes at 1.86 degrees lower EXAMPLE 1: A 1.0 m glucose solution freezes at -1.86 degrees Celsius EXAMPLE 2: Plasma freezes at -0.56 degrees Celsius, therefore plasma is 0.3 Osm.

24. Tonicity Tonicity is the effect of solute concentration on the osmotic movement of water. Isotonic – same solute on both sides. Hypotonic – a lower solute concentration, lower osmotic pressure Hypertonic – has a greater osmotic pressure crenation

25. Tonicity, cont Tonicity takes into account the permeability of the membrane to the solutes. If the solutes can cross the membrane, the tonicity will change. 1)If you place RBCs in a 0.3m solution of urea, the tonicity will not be isotonic. Urea can cross into the RBCs and draw water with it. 2)These cells will eventually burst. 3)Therefore, 0.3 m urea is isoosmotic but not isotonic isosmotic – solutions that have the same osmolality

26. Figure 6.14 - Homeostasis of plasma concentration Osmoreceptors (neurons) in the hypothalamus lose water due to osmosis when a person is dehydrated. The neurons shrink, causing a mech- anical stiumulation of the receptor, which triggers: a.Thirst b.Decreased excretion of water in urine due to ADH secretion

27. Carrier-Mediated Transport.

28. no ATP used Net movement from high to low Requires specific carrier proteins Facilitated Diffusion of Glucose

29. Isoforms: a.GLUT1 – CNS b.GLUT2 – pancreatic beta cells & hepatocytes c.GLUT3 – neurons d.GLUT4 – adipose tissue & skeletal muscles Unstimulated – carriers located in vesicles Stimulated – carriers fuse with plasma membrane INSERTION OF CARRIER PROTEINS INTO PLASMA MEMBRANE

30. Active Transport Review a.Low concentration to high concentration b.ATP required c.The transport protein (called a pump) is also an ATPase (Hydrolyzes ATP) d.Pump is activated by phosphorylation using a P i from ATP.

31. Located on all cells and in the ER of striated muscle cells Removes Ca 2+ from the cytoplasm The Ca 2+ Pump Fig. 6.18 An Active Transport Pump

32. a.Found in all body cells b.ATPase enzyme pumps 3 Na + out of the cell and 2 K + into the cell c.Serves three functions: 1)Provides energy for coupled transport of other molecules 2)Produces electrochemical impulses in neuron and muscle cells 3)Maintains osmolality Na + /K + Pump

33. 1)3 Na + bind to pump. 2)ATPase hydrolyzes ATP to ADP and P i which blocks both openings 3)ADP release causes a shape change that allows 3 Na + to exit pump to outside cell 4)2K + enter carrier from the outside, releasing the P i Steps of the Na + /K + pump 5) Pump returns to original shape and releases 2K + to the inside

34. Secondary Active (Coupled) Transport The Na+ gradient created by the pump results in a downhill flow of Na+ back into the cell, along with glucose Co-transport (symport) – the other molecule is moved with sodium (import of glucose) Countertransport (antiport) – the other molecule is moved in the opposite direction to Na +2 (extrusion of Ca +2 from cell) Considered Active because it relies on the Na +2 /K+ pump)

35. Transport Across Epithelial Membranes

36. Junctional complexes provide a barrier between adjacent epithelial cells Examples: tight junctions, adherens junctions, desmosomes

37. Many molecules at once Requires ATP May involve a receptor E.g. cholesterol and its transporter protein, which binds to the transporter receptor Bulk Transport

39. The Membrane Potential

40. WHAT IS MEMBRANE POTENTIAL? The cell is like a tiny battery with the positive pole outside and the negative pole inside The uneven distribution of charges between the inside and the outside of the membrane = membrane potential. Voltage is the measure of the potential difference The potential of a typical battery is 1.5 Volts.

41. Membrane Potential (Potential Difference) FIXED ANIONS ARE PHOSPHATES AND PROTEINS. K + accumulates at high concentrations in the cell because: -The Na + /K + pumps actively bring in K +. -The membrane is very permeable to K + -Negative (fixed) anions inside the cell attract K+ from outside the cell.

42. Equilibrium Potential (E) is the potential that would prevent movement of that particular ion) if the membrane were only permeable to that ion … this does not mean they are “equal” … is hypothetical The E K is -90 mV for all cells (would prevent flow of K+) Is different for each ion The E Na is +66 mV for all cells (would prevent flow of Na+) Can be calculated by the Nernst Equation Click here Click here for a video on equilibrium potential

43. Equilibrium Potential of Potassium (E K ) The E K is -90 mV for all cells (would prevent flow of K+) The electrical attraction would pull K + into the cell until it reaches a point where the concentration gradient drawing K + out matches this pull in. -- K + would reach an equilibrium, with more K + inside than outside. -- Normal cells have 150mM K + inside and 5mM K + outside.

44. Concentration of ions in the intracellular and extracellular fluids

45. Resting Membrane Potential = Resting = Membrane potential of a cell not producing any impulses.

46. Processes that influence the resting membrane potential

47. Cell Signaling

48. CELLS COMMUNICATE USING CHEMICAL SIGNALS

49. REGULATORY MOLECULES BIND TO RECEPTORS

50. Second Messengers – cAMP a.Cyclic adenosine monophosphate (cyclic AMP or cAMP) is a common second messenger. b.Steps to activate 1)A signaling molecule binds to a receptor. 2)This activates an enzyme that produces cAMP from ATP. 3)cAMP activates other enzymes. 4)Cell activities change in response.

51. FIG. 6.31 - G- Protein Cycle