Physiology Lecture (2) PDF

Physiology Organization of Cell Membrane LECTURE (2) DR. El-Sawy 0  Physiology Organization...

Physiology Organization of Cell Membrane LECTURE (2) DR. El-Sawy 0  Physiology Organization of Cell Membrane  Very thin elastic semi-permeable membrane (allowing some Definition substances to pass through it and prevent others) that surrounds cell. Thickness  7.5 nm. 1. Separates cytoplasm from ECF. 2. Maintains cell internal environment. 3. Transports of molecules into and out of the cell. 4. Controls ions distribution: Na+,K+,Ca2+,Cl- Functions 5. Contains protein receptors for hormones & transmitter substances. 6. Generates trans-membrane voltage difference i.e membrane potentials. 1. Proteins: 55%. Structure 2. Lipids: 42%. 3. Carbohydrates: 3%. DR. El-Sawy 1  Physiology Organization of Cell Membrane definition  They form the basic structure of the membrane. 1. Phospholipids : 2 layers (lipid bilayer) Head Tail  Phosphate portion.  The lipid.  Soluble in water  Insoluble in water (Hydrophilic) (Hydrophobic) Include  Face ECF and ICF.  Face each other in the interior of the bilayer. 2. Cholesterol. 3. Glycolipids. DR. El-Sawy 2  Physiology Organization of Cell Membrane intrinsic (Integral) proteins extrinsic (Peripheral) proteins  Bind to hydrophilic polar heads of lipids or Site:  Bind to hydrophobic center of the lipid bilayer  Bind to intrinsic proteins A) Transmembrane proteins: A) Peripheral proteins: Span the entire bilayer. Bind to intracellular surface of membrane → Act as: contribute to the cytoskeleton. Channels Diffusion of small, water soluble ions. B) Peripheral proteins: Bind to extracellular surface of membrane → Carriers Transport substances e.g. Glucose. Actively transport ions. contribute to the glycocalyx. Pumps Types Initiate intracellular reactions when and Receptors activated. Functions: B) Present only on one side of membrane: act as enzymes. DR. El-Sawy 3  Physiology Organization of Cell Membrane Channel and carrier functions of transmembrane proteins Pump function of transmembrane proteins Receptor function of transmembrane proteins DR. El-Sawy 4  Physiology Organization of Cell Membrane Mechanisms : Passive  It is movement of substances across the cell membrane transport down its electrochemical gradient. (Diffusion)  It is movement of substances across the cell membrane Active transport against its electrochemical gradient.  It is the process by which large sized substances are Vesicular engulfed by the cell membrane to be either : transport 1. Endocytosis: Pushed inside the cell. 2. Exocytosis: Pushed outside the cell. DR. El-Sawy 5  Physiology Organization of Cell Membrane A) Simple Diffusion : b) facilitated diffusion c) osmosis Diffusion of substances across cell membrane down its electrochemical  Passive flow of water gradient across a semi-permeable Def  by simple movement without membrane down a  With carrier proteins. carrier proteins. concentration gradient of 1. Down an electro-chemical gradient. water, i.e from 2. Passive i.e. no external energy is required. High to low 3. No carrier. 3. Need carrier protein. concentration of water or Characters 4. Not rate-limiting 4. It is rate-limited 5. Not saturable. 5. Saturable. Low to high 6. No competition 6. Competition concentration of 7. No stereospecificity 7. Stereospecificity solute. DR. El-Sawy 6  Physiology Organization of Cell Membrane  The substance binds to its carrier protein → reversible conformational change of carrier → transports of the substance across the membrane (down its Mechanism See next page. concentration gradient).  It enables the large particles to flow through the membrane e.g. glucose transport into muscle cells. DR. El-Sawy 7  Physiology Organization of Cell Membrane I) Diffusion through lipid bilayer:  The lipid soluble substance comes in contact with Diffusion of lipid- membrane at one side → dissolved in lipid bilayer → soluble transported to other side. substances  e.g. diffusion of O2, nitrogen, CO2, and alcohol.  Water: diffuses through lipid bilayer rapidly at a high rate (like a bullet) due to: Its small size. Diffusion of Its very high kinetic energy. water & other  Lipid-insoluble substances: lipid insoluble Diffusion through the membrane is markedly less than molecules that of water Examples: Urea, glucose, Na+ and K + ions. Their transport must occur through protein channels. II) Diffusion through watery protein channels:  Protein channels are highly selective for the transport of one or more specific ions or molecules because of: 1. Its diameter. 2. Its shape Selective 3. Nature of electrical charges of its inside surfaces: permeability: +ve charged channels → for passage of –ve charged particles. -ve charged channels → for passage of +ve charged particles. DR. El-Sawy 8  Physiology Organization of Cell Membrane  Example:  Na+ channel is selective for Na+ transport.  K+ channel is selective for K+ transport.  Many of the protein channels can be opened or closed by gates → control the permeability of the channels. Gating of protein  Examples: channels  Na channels: have 2 gates (outer m and inner h gates).  K+ channels: have one gate on extracellular side (n gate). Ligand-gated or chemical- Voltage-gated gated ion channels ion channels  Channels associated with a  Channels opened by changes Def membrane receptors in cell membrane potential  When the chemical agent  When the membrane binds to its receptor → potential reach certain level Mechanism of action conformational change in the → conformational change in channel → open it. the channel → open it.  Nonselective channels i.e.  Selective channel i.e. Conduct Selectivity Conduct more than one type only one ion. of similarly charged ions  Cholinergic receptors at MEP  Voltage-gated Na+, K+ and Example of skeletal muscle Ca+ channels on membrane of a nerve.  Generation of MEP potential  Generation of action Significance & postsynaptic potentials. potential. DR. El-Sawy 9  Physiology Organization of Cell Membrane DR. El-Sawy 10  Physiology Organization of Cell Membrane  The difference between the rate of diffusion of a substance in Def both directions (outside and inside). a) The concentration gradient for the solute. b) The diffusion coefficient of the membrane. Factors c) The membrane surface area. affecting The rate of diffusion is directly proportional to these factors. d) Membrane thickness : The rate of diffusion is inversely proportional to membrane thickness.  Flux (net rate of diffusion of substance)= 𝑫. 𝑨 − (𝑪𝒊𝒏 − 𝑪𝒐𝒖𝒕) 𝑿 D = diffusion coefficient. A = area of membrane (cm2). Equation X = thickness of the membrane (cm). Cin and Cout = the concentration of the material on the inside and outside of the membrane, respectively (mmol/L). The -ve sign indicates that the material is moving down its concentration gradient. DR. El-Sawy 11  Physiology Organization of Cell Membrane Osmolarity Tonicity  It is the expression of concentration in osmoL/L.  The ability of the particles to cause a change in  A property of a solution and is independent of the cell volume. any membrane.  Used to describe the osmolarity of a solution Definition  It depends on the total number of particles in relative to plasma & effect of this solution on cell solution, independent of mass, charge, or chemical size. composition. Isotonic Hypotonic Hypertonic solution solution solution Same Osmolarity Osmolarity less Hypo-osmotic Iso-osmotic Hyper-osmotic osmolarity as higher than Same osmolarity than plasma Less than More than plasma plasma Types as plasma (290- plasma plasma No change in 300mosm/L) Drawing water Drawing water cell volume e.g. into cell → cell out of cell → Nacl solution swelling. cell shrinkage. 0.9 %.  One particle of each of the following has the NB same osmolarity: Cl-, Na+, glucose, urea. DR. El-Sawy 12  Physiology Organization of Cell Membrane  Movement of substances across the cell membranes against an Def electrochemical gradient. 1. Occurs against the electrochemical gradient (uphill). 2. Active i.e. energy is required. Characters 3. Requires carrier protein, so exhibits specificity, saturation, & competition. A) Primary active transport Types B) Secondary active transport DR. El-Sawy 13  Physiology Organization of Cell Membrane Obtain its energy directly from the hydrolysis of ATP. Examples : Na+-K+ ATPase Ca2+-ATPase K+-H+-ATPase (Na+-K+ pump) (Ca2+-pump) (proton pump)  Cell membranes.  Sarcoplasmic  Stomach parietal- Site reticulum & cell cells. membranes.  Transports 3 Na+  It maintains low  It transports H ions from ICF to ECF & intracellular Ca into lumen. Impo. 2 K+ from ECF to ions concentration. ICF.  Digitalis (Digoxin)  Proton pump Inhibited inhibitors by (omeprazole) DR. El-Sawy 14  Physiology Organization of Cell Membrane Sodium-potassium pump (Na-K ATPase) Site  Present in the cell membranes.  It is formed of 4 subunits (2α and 2 β) : β subunits anchoring subunits. ATPase activity → cleave ATP & release energy. α subunits Binding sites for 3 Na → on intracellular side. Binding sites for ATP → on intracellular side. Composition Binding sites for 2 K → on extracellular side. A) Phosphorylation step When 3 ions of Na+ and ATP molecule bind to α subunit, → its ATPase hydrolyses ATP into ADP + Pi + Energy. This energy is used to phosphorylate α subunit to form α subunit phosphate bond → conformational change in α Steps subunit → transport 3 Na+ to the exterior. B) De-phosphorylation step When 2 ions of K+ bind to the α subunit → the α subunit phosphate bond hydrolyzes → another conformational change → transports of 2 K+ ions to the interior. 1. It transports Na+ from ICF to ECF and K+ from ECF to ICF. This Significance maintains low intracellular Na+ and high intracellular K+. 2. It utilizes about 40% - 50% of energy. DR. El-Sawy 15  Physiology Organization of Cell Membrane DR. El-Sawy 16  Physiology Organization of Cell Membrane Def :  It is a type of an active transport which use the energy stored in the Na concentration gradient. Examples : Na+-glucose co-transport Na+-Ca2+ exchange  The luminal membrane of  Many cell membranes (as Site intestinal mucosal and renal ventricular muscles cells). proximal tubule cells.  Transports Ca2+ uphill from low intracellular Ca2+ to high Mechanism extracellular Ca2+ and Na move in opposite directions across the cell membrane. If solutes move in same direction across cell membrane : → it is called cotransport or symport (e.g. Na+ - glucose transport). If solutes move in opposite directions across cell membranes : → it is called counter-transport or antiport (e.g. Na+-Ca2+ & Na+-H+). DR. El-Sawy 17  Physiology Organization of Cell Membrane Comparison between simple diffusion, facilitated diffusion & active transport Facilitated Simple diffusion Active transport diffusion Electrochemical Downhill Downhill Uphill gradient Does not need Does not need Energy Needs energy energy energy Rate Not limited Limited Limited Saturation Not Saturable Saturable Saturable Carrier Not need carrier Needs carrier Needs carrier Not show Competition Shows competition Shows competition competition Stereo- Does not depend on Depends on Depends on specificity stereospecificity Stereospecificity Stereospecificity DR. El-Sawy 18  Physiology Organization of Cell Membrane  Mechanism by which the large sized substances can cross the Def cell membranes. Types  Def : The extracellular material is trapped within vesicles that are formed by invagination of the cell membrane & The endocytic vesicles detached from the cell membrane.  Types: Endocytosis 1. Receptor mediated endocytosis: e.g. iron & cholesterol. 2. Phagocytosis: is the endocytosis of solid particles e.g. bacteria and dead tissue. 3. Pinocytosis: is the endocytosis of substances in solution e.g. proteins  Def: The intracellular material is trapped within vesicles → then Exocytosis the vesicles fuse with the cell membrane → release their (cell contents to the ECF. vomiting)  e.g. release of synaptic transmitters and hormones. DR. El-Sawy 19