1. Cellular Communication Transport across cell membrane Lecture 2 Page 63-76

2. Arrangement of Membrane Proteins Plasma membrane consists of a lipid bilayer - made up of phospholipids, cholesterol and glycolipids. Membrane proteins belong to different groups: ―Integral proteins - extend into or through the lipid bilayer ―Transmembrane proteins - most integral proteins, span the entire lipid bilayer ―Peripheral proteins - attached to the inner or outer surface of the membrane, do not extend through it

3. Functions of Membrane Proteins Ion channel Transporter Receptor

4. Functions of Membrane proteins Enzyme Cell Identity Marker Linker

5. Membrane Permeability The cell is either permeable (allow to go through) or impermeable to certain substances. The lipid bilayer is permeable to non polar and uncharged molecules like oxygen, carbon dioxide, water and steroids, but impermeable to polar and charged molecules (glucose). Transmembrane proteins act as channels and transporters to assist the entrance of certain substances, for example, glucose and ions

6. Gradient Across Cell Membrane The selective permeability of the plasma membrane allows the cell to maintain different concentrations of certain substances on either side of the plasma membrane. This constitute chemical gradient There is more K+ inside the cell (intracellular fluid) than outside the cell. There is more Na+ outside the cell (extracellular fluid) than inside the cell. The inner side of the plasma membrane is more negatively charged while the outer side is more positively charged. This constitute electrical gradient. The combined influence of two gradients is called electrochemical gradient Down concentration gradient = down hill (from high to low concentration) Up concentration gradient = up hill (from low to high concentration)

7. Gradient Across Cell Membrane 1.Chemical Gradient (from high to low concentration) 2. Electrical gradient (for + ions From more positive to less Positive and vice versa) ELECTROCHEMICAL GRADIENT 1 and 2 together called

8. Transport Processes Passive processes - substances move across cell membranes without the input of any energy; use the kinetic energy of individual molecules or ions Active processes - a cell uses energy, primarily from the breakdown of ATP, to move a substance across the membrane, i.e., against a concentration gradient

9. Passive Processes 1.Simple diffusion through lipid bilayer 2.Diffusion through channels 3.Facilitated diffusion Active Processes 1.Pumps Endocytosis and exocytosis Transport Processes

10. Principles of Diffusion Is a passive process in which the random mixing of particles in a solution occur because of the particles kinetic energy. Occurs down the concentration gradient. Factors influencing diffusion rate: Steepness of concentration gradient Temperature Mass of diffusing substance Surface area Diffusion distance

11. Copyright 2009 John Wiley & Sons, Inc. Osmosis Net movement of water through a selectively permeable membrane from an area of high concentration of water (lower concentration of solutes) to one of lower concentration of water Water can pass through plasma membrane in 2 ways: 1.through lipid bilayer by simple diffusion 2.through aquaporins, integral membrane proteins

12. Tonicity and its effect on RBCS Tonicity: is the measure of solution ability to change the volume of cells by altering their water contents. Isotonic solution: doesn't not change the shape of the cell because water molecules enter and exit the cell at the same rate. Hypotonic solution: (less concentration of solutes than in the cytosol ) more water enters the cell causing lysis if cell. Hypertonic solution: (more concentration of solutes than in the cytosol ) more water leaves the cell causing shrinkage of cells (crenation). 0.9% NaClwatersea water Intravenous solutions: 0.9% NaCl, 5% dextrose (5DW)

13. Simple Diffusion and Facilitated Diffusion Simple diffusion : through lipid bilayer without help of membrane protein. Facilitated diffusion: Integral mebrane proteins assist in moving substances (charged or too polar) Facilitate diffusion are: ―Ion channel mediated ―Carrier mediated

14. Copyright 2009 John Wiley & Sons, Inc. Channel-mediated Facilitated Diffusion of Potassium ions through a Gated K + Channel

15. Copyright 2009 John Wiley & Sons, Inc. Carrier-mediated Facilitated Diffusion of Glucose across a Plasma Membrane Glucose transporter Glucose gradient Glucose Extracellular fluid Plasma membrane Cytosol 1 2 3

16. Active Transport Active transport: Solutes are transported across plasma membranes with the use of energy, from an area of lower concentration to an area of higher concentration.  Primary active transport: Uses energy obtained from hydrolysis of ATP Eg. Na + /K + pump.  Secondary active transport: A carrier molecule uses energy stored in ionic concentration difference of one substance to move another substance. Two types of carrier molecules:  Symporters: Move two substances in the same direction Na-glucose symporter absorbs both substances from Intestine.  Antiporters: Move substances in opposite direction (Na + /Ca 2+ antiporter regulate cell calcium by expelling from the cell. Na + /H + antiporter regulate cell pH by expelling H +

17. Copyright 2009 John Wiley & Sons, Inc. Primary Active Transport Active transport: Solutes are transported across plasma membranes with the use of energy, from an area of lower concentration to an area of higher concentration. The Na+/K+ pump (Na-K ATPase) expels 3 Na + and brings in 2 K + Its Primary active transport because it uses energy in the shape of ATP 1 3 Na + expelled 3 Na + ADP P P 2 K + imported K + gradient Na + gradient Na + /K + ATPase Extracellular fluid Cytosol 2K + ATP 234

18. Secondary Active Transport How digitalis ( a drug given to patients with heart failure) inhibits Na+/K+. Explain how it increases Calcium in heart muscle.

19. K Na Na-K pump Na-Ca exchanger Digoxin X Ca Na Ca 2+ Inhibition of Na-K pump increases intracellular calcium CARDIAC MUSCLE Inhibition of Na-K pump increases Na+ concentration inside the cell The gradient for Na+ entry through Na-Ca exchanger decreases Less Na+ enters and therefore more Ca2+ remains inside the cardiac muscle This increases the strenght of contraction of a weak muscle

20. Copyright 2009 John Wiley & Sons, Inc. Transport in Vesicles Vesicle - a small spherical sac formed by budding off from a membrane. They import and export material into and out of the cell, through a process that is ATP dependent. Endocytosis - materials move into a cell in a vesicle formed from the plasma membrane 1. Receptor-mediated endocytosis - phagocytosis - bulk-phase endocytosis (pinocytosis) 2. Exocytosis: vesicles fuse with the plasma membrane, releasing their contents into the extracellular fluid (hormones, digestive enzymes, neurotransmitters) 3. Transcytosis: a combination of endocytosis and exocytosis

21. Receptor Mediated Endocytosis Also HIV virus enters T-cell by endocytosis after attaching to a receptor called CD4 Cells use Cholesterol to rebuild its membranes and for synthesis of steroids. LDL=Low density lipoprotein

22. Phagocytosis Phagocytosis is carried out by phagocytes: macrophages and neutrophils (white blood cells). Is a vital defense mechanism through which invading microbes are destroyed. Particle binds to receptor on plasma membrane Phagocyte extends pseudopods to surround the partcle. Membrane fuse to form a phagosome Phagosome fuse with lysosome Lysosome enzymes digest the particles. The undigested material remain in the residual body.

23. Bulk-phase Endocytosis (Pinocytosis) No receptors involved Tiny droplets of extracellular fluid are taken into the cell. Resulting smaller molecules leave lysosome to be used else where in the cell. Occurs in most cells specially absorptive cells in the intestine and kidneys.