Ch 5 Membrane Dynamics Cell membrane structures and

Ch 5: Membrane Dynamics Cell membrane structures and functions – Mass balance and homeostasis – Diffusion – Protein-mediated transport – Vesicular transport – Transepithelial transport – Osmosis and tonicity – (The resting membrane potential)

Mass Balance • Law of mass balance applies to human body • 2 options for output: Fig 5 -2 – Excretion – Metabolism (production of metabolites) • Liver is major organ for clearance • Other ways to clear molecules: Kidneys, saliva, sweat, breast milk, hair, lungs

Homeostasis • Body’s ability to maintain relatively stable internal environment (dynamic steady state!) • H 2 O is in osmotic equilibrium (free movement) • Yet: selective permeability of cell membrane leads to chemical and electrical disequilibrium between ECF and ICF • Whole body is electrically neutral

Transport Across Cell Membrane Cell membrane is selectively permeable Permeability is variable Relevant properties of membrane - Availability of transport proteins - Cholesterol content Relevant properties of molecule - Size and - Charge (lipid solubility) Passive vs. active transport

Properties of Diffusion Passive – based on inherent Ekin of all molecules In open system or across partitions Net movement down chemical / conc. gradient until state of equilibrium reached Direct correlation to temperature (why? ) Indirect correlation to molecule size Slower with increasing distance

Distance – Time Relationship Time for diffusion to progress to given distance ~ to distance squared diffusion over 100 m takes 5 sec. diffusion over 200 m takes ? ? diffusion over 400 m takes ? ? diffusion over 800 m takes ? ? Diffusion effective only over short distances!

Simple Diffusion • Movement of lipophilic molecules directly through phospholipid bilayer. E. g. ? • Diffusion rate 1 Thickness of membrane • Diffusion rate to membrane surface area

Fig 5 -6 Fick’s law of Diffusion rate surface area x conc. gradient X membrane permeability membrane thickness

Protein Mediated Transport For all lipophobic molecules Two mediated transport categories: 1. Passive transport (facilitated diffusion) 2. Active transport Two categories of transporter proteins 1. Channel proteins (rapid but not very selective – for small molecules only) 2. Carrier proteins (slower but very selective – also for large molecules) Three other functions of membrane proteins Fig 5 -7

Channel Proteins • For small molecules e. g. ? • Aquaporins • > 100 ion channels • Selectivity based on diameter and ________ • All have “gate” region Fig 5 -10

Open Channels vs. Gated Channels = pores Gates closed most of the time Have gates, but gates are open most of the time. Chemically gated channels (controlled by Also referred to as “leak channels”. Voltage gated channels (controlled by messenger molecule or ligand) electrical state of cell) Mechanically gated channels (controlled by physical state of cell: temp. ; stretching of cell membrane etc. )

Carrier Proteins (2 nd type of transport protein) Compare to Fig 5 -13 • Never form direct connection between ECF and ICF • Bind molecules and change conformation • Used for small organic molecules (such as? ) • Ions may use channels or carriers • Rel. slow (1, 000 to 1 Mio / sec)

Uniport vs. Cotransport Symport Molecules are carried in same direction Examples: Glucose and Na+ Antiport Molecules are carried in opposite direction Examples: Na+/K+ pump

Facilitated Diffusion Form of carrier mediated, passive transport Some characteristics same as simple diffusion but also: • specificity • competition • saturation More later Fig 5 -14

Summary: Passive Transport = Diffusion (Def? ) – 3 types: 1. Simple diffusion 2. Osmosis 3. Facilitated diffusion (= mediated transport)

Active Transport • • Movement from low to high conc. ATP needed Creates state of ____ equilibrium Primary (direct) active transport – ATPases or “pumps” (uniport and antiport)– examples? • Secondary (indirect) active transport – Symport or antiport

1 o Active Transport • ATP energy directly fuels transport • Most important example: Na+/K+ pump = sodium-potassium ATPase (uses up to 30% of cell’s ATP) • Establishes Na+ conc. gradient Epot. can be harnessed for other cell functions Fig 5 -17 ICF: high [K+], low [Na+] ECF: high [Na+], low [K+] Fig 5 -16

Secondary Active Transport • Indirect ATP use: uses Epot. stored in conc. gradient • Coupling of Ekin of one molecule with movement of another molecule • Example: Na+ / Glucose symporter Fig 5 -18 other examples • 2 mechanisms for Glucose transport

Specificity, Competition, and Saturation characterize Carrier-Mediated Transport • Specificity (e. g. : GLUT transporters for hexoses) • Competition (competitive inhibition applied in medicine, e. g. : gout) • Saturation (numbers of carriers can be adjusted)

Vesicular Transport Movement of large molecules across cell membrane: 1. Phagocytosis 2. Endocytosis – Pinocytosis – Receptor mediated endocytosis – Potocytosis 3. Exocytosis

Phagocytosis • Requires energy • Cell engulfs particle into vesicle via pseudopodia formation • E. g. : some WBCs engulf bacteria • Vesicles formed are much larger than those formed by endocytosis • Phagosome fuses with lysosomes ? (see Fig. 5 -23)

Endocytosis Requires energy No pseudopodia - Membrane surface indents Smaller vesicles Nonselective: Pinocytosis for fluids & dissolved substances • Selective: • • – Receptor Mediated Endocytosis via clathrin-coated pits - Example: LDL cholesterol and Familial Hypercholesterolemia Fig 5 -24 – Potocytosis via caveolae

Exocytosis Intracellular vesicle fuses with membrane Requires energy and Ca 2+ Examples: goblet cells, fibroblasts; receptor insertion; waste removal

Movement through Epithelia: Transepithelial Transport Uses combination of active and passive transport Molecule must cross two phospholipid bilayers Polarity of epithelial cells → Apical and basolateral cell membrane has different proteins: Na+- glucose transporter on apical membrane Na+/K+-ATPase only on basolateral membrane Fig 5 -26

Transcytosis • Endocytosis vesicular transport exocytosis • Moves large proteins intact • Examples: – Absorption of maternal antibodies from breast milk – Movement of proteins across capillary endothelium

Osmosis Compare to Fig. 5 -29 Movement of water down its concentration gradient. Opposes movement Osmotic of water pressure across membrane Water moves freely in body until osmotic equilibrium is reached

Molarity vs. Osmolarity In chemistry: • Mole / L • Avogadro’s # / L In Physiology Important is not # of molecules / L but # of particles / L: osmol/L or Os. M Why? Osmolarity takes into account the dissociation of molecules in solution

Convert Molarity to Osmolarity = # of particles / L of solution • 1 M glucose = ? Os. M glucose • 1 M Na. Cl = ? Os. M Na. Cl • 1 M Mg. Cl 2 = ? Os. M Mg. Cl 2 • Osmolarity of human body ~ 300 m. Os. M • Isosmotic, hyperosmotic, hyposmotic

Tonicity • Physiological term describing volume change of cell if placed in a solution • Always comparative. Has no units. – Isotonic – Hypertonic – Hypotonic • Depends not just on osmolarity (conc. ) but also on nature of solutes (penetrating vs. nonpenetrating solutes)

Penetrating vs. Nonpenetrating Solutes • Penetrating solute: can enter cell (glucose, urea) • Nonpenetrating solutes: cannot enter/leave cell (sucrose, Na. Cl*) • Determine relative conc. of nonpenetrating solutes in solution and in cell to determine tonicity. – Water will move to dilute nonpenetrating solutes – Penetrating solutes will distribute to equilibrium Fig 5 -31

IV Fluid Therapy 2 different purposes: – Get fluid into dehydrated cells or – Keep fluid in extra-cellular compartment

Resting Membrane Potential IC and EC compartments are in electrical disequilibrium Review basics of electricity if necessary K+ is major intracellular cation Na + is major extracellular cation Water = conductor / cell membrane =

Electro-Chemical Gradients • Allowed for by cell membrane • Created via – Active transport – Selective membrane permeability to certain ions and molecule Fig 5 -32 • Membrane potential = unequal distribution of charges across cell membrane

Resting Membrane Potential Difference • All cells have it • Resting cell at rest (all cells) • Membrane Potential separation of charges creates potential energy • Difference difference between electrical charge inside and outside of cell (ECF by convention 0 m. V) • Measuring membrane potential differences Fig 5 -33

Resting Membrane Potential Mostly Due to Potassium Cell membrane – impermeable to Na+, Cl - & Pr – – permeable to K+ moves down concentration gradient (from _____ to ______ of cell) Excess of neg. charges inside cell Electrical gradient created Neg. charges inside cell attract K+ back into cell

Equilibrium Potential for K+ Eion= Membrane potential difference at which movement down concentration gradient equals movement down electrical gradient In other words: At Eion: electrical gradient equal to and opposite concentration gradient EK+ = - 90 m. V Fig 5 -34

Equilibrium Potential for Na+ • Assume artificial cell with membrane permeable only to Na+ • Redistribution of Na+ until movement down concentration gradient is exactly opposed by movement down electrical gradient ENa+ = + 60 m. V Fig 5 -35

Resting Membrane Potential In most cells between -50 and -90 m. V (average ~ -70 m. V) Reasons: • Membrane permeability: > Na+ at rest • Small amount of Na+ leaks into cell • Na+/K+-ATPase pumps out 3 Na+ for 2 K+ pumped into cell K+

Changes in Ion Permeability • lead to change in membrane potential • Terminology: Stimulus Depolarization Repolarization Hyperpolarization Fig 5 -37

Explain • Increase in membrane potential • Decrease in membrane potential • What happens if cell becomes more permeable to potassium • Maximum resting membrane potential a cell can have

Insulin Secretion • Membrane potential changes play important role also in non-excitable tissues! • -cells in pancreas have two special channels: – Voltage-gated Ca 2+ channel – ATP-gated K+ channel Fig 5 -38

Cells Avoid Reaching Glucose Equilibrium ? ? ?

Running problem: Cystic Fibrosis