1. Chapter 6 Interaction Between Cells & Extra-cellular Environment Remon Wahba, MD

2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 6 Outline  Extra-Cellular Environment  Movement Across Plasma Membrane  Osmosis  Membrane Transport Systems  Membrane Potential  Cell Signaling 6-2

3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cells & The Extra-Cellular Environmentr  Water, Ions and other molecules are present in our body in TWO Compartments:  Intracellular = inside the cells  Extracellular = outside the cells  There is always interaction between the two compartments (movement of Ions and Molecules)

4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Body Water  Water in our body is distributed between:  The Intracellular Compartment  67% of total body H 2 0  The Extracellular Compartment (ECF)  33% of total body water is outside cells  20% of ECF is Blood Plasma  80% of ECF is Interstitial Fluid  Present in between the cells  Contained in gel-like matrix 6-4

5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Extracellular Matrix  Is a meshwork of Collagen & Elastin fibers linked to molecules of gel-like ground substance & to plasma membrane integrins  Glycoprotein adhesion molecules that link Intracellular & Extracellular compartments Fig 6.1 6-5

6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. A Simplified Body Plan

7. Movement Across Plasma Membrane 6-6

8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transport Across Plasma Membrane  Plasma membrane is Selectively Permeable--allows only certain kinds of molecules to pass  Two main types of transport:  Passive transport  Moves compounds down concentration gradient  Requires No Energy  Includes Diffusion, Osmosis, Facilitated Diffusion  Active transport  Moves compounds against concentration gradient  Requires Energy & transporters

9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transport Across Plasma Membrane  Two major categories:  Non-carrier mediated transport  Occurs by Diffusion, Osmosis  Carrier-Mediated transport  Requires specific protein transporters & Channels  Includes Facilitated Diffusion & Active Transport

10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion  Is caused by random motion of molecules  Net movement is from regions of High Concentration to regions of Low Concentration OR  Movement down the concentration gradient

11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion

12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion  Concentration  Number of molecules in a given unit of volume  Gradient  Physical difference between two regions

13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Non-polar compounds diffuse readily through the cell membrane  Also some small polar molecules including C0 2 & H 2 0  Gas exchange occurs by Diffusion Diffusion (continued) 6-10

14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion (continued)  Cell membrane is Impermeable to charged & most polar compounds  Charged molecules must have:  Ion Channels OR  Protein Transporters to move across the membrane

15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion (continued)  Rate of diffusion depends on:  Magnitude of the concentration gradient  Permeability of the membrane  Temperature  Surface area of the membrane 6-11

16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diffusion (continued)  Diffusion of H 2 0 Molecules is called Osmosis

17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Osmosis  Is net diffusion of H 2 0 across a selectively permeable membrane  H 2 0 diffuses down its concentration gradient  H 2 0 is less concentrated where there are more solutes  Solutes have to be Osmotically Active  i.e. cannot move freely across the membrane

18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Osmosis

19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  H 2 0 diffuses Down its Concentration Gradient until its concentration is equal on both sides of membrane Osmosis continued 6-14

20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Is the Force that would have to be exerted to stop osmosis  Indicates how strongly H 2 0 wants to diffuse Solute Concentration  Is proportional to Solute Concentration  The more concentration of the solute, the more is the Osmotic Pressure Osmotic Pressure 6-15

21. Molarity & Molality

22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molarity & Molality  The Molecular weight of a molecule is the sum of the Atomic Weights of its atoms

23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molecular Weights  NaCl:  Na = 23.0  Cl = 35.5 = 58.5  Glucose:  C6 = 12x6 = 72  H12 = 1x12 =12  O6 = 16x6 = 96 =180

24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. mole mole  An amount of any compound equal to its molecular weight in grams is called mole and it contains a fixed number of molecules.  Avogadro’s number:  Number of molecules present in a mole  It is equal to 6.02 X 10 23

25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. mole  So one mole of Nacl contains the same number of molecules as one mole of Glucose  (They are different in weight but they contain the same number of molecules).  = Avogadro’s number

26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molarity & Molality  One molar solution (1.0M) =  One mole of solute dissolved in water to make 1L of solution  Doesn't specify exact amount of H 2 0  One molal solution (1.0m) =  One mole of solute dissolved in 1 L (1KG) of H 2 o  Measurement of concentration of solutes (number of molecules) in solutions 6-16

27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molarity & Molality

28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molarity & Molality  Osmolality (Osm)  is total Molality of a solution  Depends on number of molecules or particles  NaCl dissociates into Na + & Cl -  So1.0 molal solution of NaCl yields a 2 Osm solution ( has double the osmolality of 1 molal solution of glucose

29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Molarity & Molality

30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Tonicity  Is the effect of a Solution on the Osmotic Movement of H 2 0

31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Tonicity  Isotonic solutions  Have Same osmotic pressure as Plasma  E.g. 5% Dextrose & 0.9% NaCl  Hypertonic solutions  Have Higher osmotic pressure than Plasma  Water moves to the outside of Cells  Hypotonic solutions  Have Lower osmotic pressure than Plasma  Water moves to the inside of Cells

32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Effects of tonicity on RBCs Fig 6.11 shrink 6-19

33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Blood Osmolality  Blood Osmolality is maintained in a narrow range around 300m Osm  In cases of dehydration, Osmoreceptors in Hypothalamus are stimulated leading to:  ADH Release  Which causes kidney to conserve H 2 0  Thirst  To increase water intake

34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Blood Osmolality

35. Membrane Transport Systems 6-21

36. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carrier-Mediated Transport  Molecules, Too Large to diffuse are transported across the cell membrane by  Protein Carriers 6-22

37. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carrier-Mediated Transport continued  Protein Carriers exhibit:  Specificity for single molecule  Competition among substrates for transport  Saturation when all carriers are occupied  This is called T m (transport maximum) 6-23

38. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Facilitated Diffusion  Is Passive Transport down concentration gradient by: carrier proteins 6-24

39. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Active Transport  Is Transport of molecules Against a Concentration Gradient  Requires Energy (ATP) 6-25

40. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Na + /K + Pump  Uses ATP to move  3 Na + out &  2 K + in Against their gradients Fig 6.17 6-26

41. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Secondary Active Transport  Uses energy from “downhill” transport of Na + to drive “uphill” movement of another molecule  Also called Coupled Transport  ATP required to maintain Na + gradient  Important for Oral Rehydration  Glucose helps the absorption of Na+ then water follows by osmosis 6-27

42. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Absorption is transport of digestion products across intestinal epithelium into blood  Reabsorption transports compounds out of urinary filtrate back into blood Fig 6.19 Transport Across Epithelial Membranes 6-29

43. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transport Across Epithelial Membranes continued  Transcellular Transport  Moves material from 1 side of Epithelial Cells to the other (Through the Cell)  Paracellular Transport  Moves material through tiny spaces between Epithelial Cells 6-30

44. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Bulk Transport  Movement of Large Molecules & Particles across plasma membrane  Occurs by Endocytosis & Exocytosis (Ch 3) 6-31

45. Membrane Potential 6-32

46. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Membrane Potential  Is difference in Electric charge across the Plasma Membrane  The inside of the cell is Negatively charged compared to the outside Fig 6.22 6-33

47. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Resting Membrane Potential (RMP)  Is membrane voltage of cell in unstimulated state (undisturbed)  RMP of most cells is -65 to –85 mV  RMP depends on:  Concentrations of ions inside & outside  Permeability of each ion  Affected most by K + because it is more permeable 6-38

48. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Resting Membrane Potential (RMP)  Results from:  LARGE NEGATIVELY CHARGED organic molecules inside the cell  Na+ / K+ pump  Three Na+ are pumped out  Two K+ are pumped in  The Plasma Membrane is more permeable to K+ than Na+

49. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Some Na + diffuses in so RMP is less negative than E K+ Fig 6.25 Resting Membrane Potential (RMP) continued 6-39

50. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Role of Na+/K+ Pumps in RMP  Because 3 Na+ are pumped out for every 2 K+ taken in, pump is Electrogenic  It adds about - 3mV to RMP Fig 6.26 6-40

51. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Resting Membrane Potential (RMP)

52. Cell Signaling 6-41

53. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Signaling  Cells communicate with each other  Two main ways:  Chemical messengers: To respond to a chemical signal, the target cell must have a Receptor protein specific for chemical messenger  Paracrine  Hormones (Endocrine)  Neurotransmitters  Electric communication:  Gap Junctions

54. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Signaling  In Paracrine signaling, cells secrete regulatory molecules that diffuse to nearby target cells

55. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Signaling  In Endocrine signaling, cells secrete chemical regulators that move through Blood Stream to distant target cells

56. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Signaling  In Synaptic signaling, A neuron sends messages using Neurotransmitter to another cell via synapses

57. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cell Signaling continued  Some use Gap Junctions through which signals pass directly from one cell to the next