There should be nothing new for you in this lecture. If there is, stay for office hours and / or ask for help from the TAs.

Transcription

1 Membranes 02 The goal of this lecture is to review pre-requisite material related to the structure and function of biological membranes and to provide students a further overview of material to be covered in the course. The sections for this lecture are: Structure of biological membranes Function of biological membranes Examples of biological membranes Life is a series of chemical reactions occurring in compartmentalized environments. The main purpose of life to kee itself alive Physiology, the study of how life works, is based on the simultaneous occurrence of the following three concepts: levels of organization structure / function relationship homeostatic regulation There should be nothing new for you in this lecture. If there is, stay for office hours and / or ask for help from the TAs. Course Outline Topic # Topic lecture Silverthorn Week 1 to week 2 Topic #1 Topic #2 Introduction (pre-requisite material) Membranes (pre-requisite material) Pre-requisite Material (chapter # 5) Topic #3 Homeostasis and Signal Transduction 6 lectures, Topic #4 Endocrine Communication and the Endocrine System 7 recitations, Topic #5 Neural Communication and the Sensory System 8-11 office hours, review, Topic #6 Muscle, Muscle Contraction and their Regulation exam1 (chapter # 8) REVIEW #1 material from topic #01 #06 EXAM #1 material from topic #01 #06 (33%) Week 3 to week 4 Topic #7 Topic #8 Basic Physiology of the Cardiovascular System Basic Physiology of the Respiratory System lectures, recitations, review, exam2 Topic #9 Basic Physiology of the Renal System (chapter # 7) REVIEW #2 material from topic #01 #09 EXAM #2 material from topic #01 #09 (33%) Week 5 to week 6 Topic #10 Topic #11 Basic Physiology of the Gastrointestinal System Food Intake, Metabolism, Energy Balance and Exercise lectures, recitations, review, exam3 Topic #12 From Sexual Differentiation to Adult Reproduction 26 (chapter # 6) REVIEW #3 material from topic #01 #12 EXAM #3 material from topic #01 #12 (33%) (all tests are cumulative) 1

2 Physiology ( how to study ) The following slides show how to review prerequisite material for this course. Slides are only an attempt to guide students to important aspects of each topic. UNDERSTANDING these topics will depend on your background linked to this course prerequisite material (e.g. its biology, physics and chemistry). The course material will be presented in a similar fashion. You will need to read ahead each lecture material in your textbook and any extra sources you may use, and my lectures will only highlight the most important concepts you must attempt to UNDERSTAND. Since there is so much material in this course, it will be impossible for you to memorize all of it. Thus, you need to UNDERSTAND each important topic and rank its importance in relation to the overall course material. Membranes ( functions ) Functions of Cell Membranes (membranes are phospholipids bilayes interspersed with proteins) 2

3 Membranes ( structure ) (membranes are phospholipids bilayes interspersed with proteins) Membranes ( structure ) membranes are phospholipid bilayers interspersed with associated proteins having transmembrane hydrophobic domains (liposoluble domains) some of these proteins are ion channels (e.g. Na, K, Cl, Ca) some of these proteins are transporters (e.g. GLUT 1-5) (membranes are phospholipids bilayes interspersed with proteins) 3

4 Membranes ( structure ) (membranes are phospholipids bilayes interspersed with proteins) Membranes ( structure ) (membranes are phospholipids bilayes interspersed with proteins) 4

5 Membranes ( structure ) (membranes are phospholipids bilayes interspersed with proteins) Membranes ( structure ) (membranes are phospholipids bilayes interspersed with proteins) 5

6 Membranes ( structure ) (membranes are phospholipids bilayer interspersed with proteins) Membranes ( phospholipids ) (examples of products derived from membrane phospholipids) (membranes are phospholipids bilayes interspersed with proteins) 6

7 Membranes ( proteins ) Membranes ( channels ) some proteins are ion channels 7

8 Membranes ( channels ) some proteins are ion channels Membranes ( transporters ) some proteins are transporters 8

9 Membranes ( transporters ) Membranes ( structure ) some proteins are - ion channels - transporters 9

10 Membranes ( receptors ) membranes are phospholipid bilayers interspersed with associated proteins having transmembrane hydrophobic domains (liposoluble domains) other proteins are receptors (e.g. G protein-linked receptors) other proteins are enzymes and / or receptors (e.g. adenyl-cyclase enzyme / tyrosine-kinase receptors) seven - transmembrane domain receptors ECF plasma memb. ICF COOH ß - adrenergic and glucagon receptors among many others N H 2 G Membranes ( receptors ) other proteins are receptors 10

11 Membranes ( receptors ) kinase Cys rich Cys residues hydrophobic aa N H2 ECF other proteins are enzymes and / or receptors EGF insulin single - tm PDGF domain receptors ANP ICF JAK2 GH, Prl, cytokines COOH Membranes ( functions ) 11

12 Membranes ( functions ) Membranes ( functions ) simple diffusion, diffusion of solutes if membrane is permeable, Fick's first law of diffusion J= -DA dc/dx J= net rate diffusion, moles or grs per unit time A= area of the plane dc/dx= concentration gradient across plane D= diffusion coefficient (proportionality cte) osmosis, water diffusion through memb. impermeable to ions, van't Hoff's law for osmotic pressure p= irtm p= osmotic pressure i= # of ions formed by dissociation of a solute R= ideal gas constant T= absolute temperature m= solute molal conc (moles solute / kg water) facilitated diffusion, diffusion of solutes through a transporter Michelis-Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport [S]= substrate concentration Vmax= max. rate of transport (influx=efflux) Km= substrate concentration for half Vmax e.g., when Km for influx = Km for efflux, equilibrium is reached at an internal concentration equal to that of the external concentration active transport, transport against concentration / electrical gradient Michelis-Menten (influx / efflux are asymetrical) V= Vmax [S] / Km + [S], V= rate of transport [S]= substrate concentration Vmax= max. rate of transport (influx efflux) Km= substrate concentration of for half Vmax e.g., when Km for influx= 0.5 mm and Km for efflux= 5 mm, equilibrium is reached at an internal concentration 10x that of the external concentration electrochemical equilibrium across a semi-permeable membrane Nernst equation Ea-Eb= -60 mv/z log10 [x]a/[x]b, Ea-Eb= ion electrochemical potential in mv z= valence of the ion (e,g., K=Na=1) [x]a= internal concentration [x]b= external concentration an electrical potential difference of about 60mV is needed to balance a 10 fold concentration difference of a univalent ion electrochemical equilibrium across a semi-permeable membrane chord conductance equation Em= gk EK/gT + gna ENa/gT + gca ECa/gT Em= membrane potential gk, gna, gca= ion conductances involved EK, ENa, ECa= ion potential equilibrium involved gt= total conductance of all ions involved expresses transmembrane electrical potential difference as a weighted average of permeable ions' equilibrium potentials involved Gibbs - Donnan equilibrium steady-state properties of a mixture of permeant (e.g., initial KCl solution inside B) and impermeant ions (e.g., initial KY solution in side A, where Y is an anion to which the plasma membrane is completely impermeable) across a semi permeable membrane Under this condition, equilibrium between the A and B sides will be reached when the product of the concentration of the permeant cation K and the permeant anion Cl is equal in side A and side B. 12

13 Membranes ( functions ) What follows is an attempt to remind you of how the physical formulas from the previous slide can be visualized under physiological conditions. All material from the next slides is prerequisite material, and is included in the first six chapters of your textbook. If you have problems with this material stay for recitation and/or talk with a TA. The specific course material starts tomorrow. Make sure that you read the assigned chapters in your textbook before tomorrow s lecture. Functions ( diffusion ) Diffusion Fick's first law of diffusion J= -DA dc/dx J= net rate diffusion, moles or grs per unit time A= area of the plane dc/dx= concentration gradient across plane D= diffusion coefficient (proportionality cte) 13

14 Functions ( osmosis ) osmosis, water diffusion through a membrane impermeable to ions, van't Hoff's law for osmotic pressure p= irtm p= osmotic pressure i= # of ions formed by dissociation of a solute R= ideal gas constant T= absolute temperature m= solute molal conc (moles solute / kg water) Functions ( osmosis ) osmosis, water diffusion through a membrane impermeable to ions, van't Hoff's law for osmotic pressure p= irtm p= osmotic pressure i= # of ions formed by dissociation of a solute R= ideal gas constant T= absolute temperature m= solute molal conc (moles solute / kg water) osmosis 14

15 Functions ( facilitated diffusion ) (e.g. Ca) (e.g. Glucose) facilitated diffusion, diffusion of solutes through a transporter Michelis - Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport [S]= substrate conc. Vmax= max. rate of transport (influx=efflux) Km= substrate conc. for half Vmax e.g., when Km for influx = Km for efflux, equilibrium is reached at an internal concentration equal to that of the external concentration Functions ( facilitated diffusion ) facilitated diffusion of solutes through a transporter Michelis-Menten (influx / efflux are symetrical) V= Vmax [S] / Km + [S], V= rate of transport [S]= substrate conc. Vmax= max. rate of transport (influx=efflux) Km= substrate conc. for half Vmax e.g., when Km for influx = Km for efflux, equilibrium reached at internal conc = to that of external conc. 15

16 Functions ( active transporter ) active transport, transport against concentration / electrical gradient Michelis-Menten (influx / efflux are asymetrical) V= Vmax [S] / Km + [S], V= rate of transport [S]= substrate concentration Vmax= max. rate of transport (influx efflux) Km= substrate concentration of for half Vmax e.g., when Km for influx= 0.5 mm and Km for efflux= 5 mm, equilibrium is reached at an internal concentration 10x that of the external concentration Functions ( active transport ) electrochemical equilibrium across a semi-permeable memb. Nernst equation Ea-Eb= -60 mv/z log10 [x]a/[x]b, (important Ea-Eb= ion electrochemical potential in mv concepts for z= valence of the ion (e,g., K=Na=1) later lectures) [x]a= internal concentration [x]b= external concentration an electrical potential difference of about 60mV is needed to balance a 10 fold concentration difference of a univalent ion electrochemical equilibrium across a semi-permeable memb. chord conductance equation Em= gk EK/gT + gna ENa/gT + gca ECa/gT Em= membrane potential gk, gna, gca= ion conductances involved EK, ENa, ECa= ion potential equilibrium involved gt= total conductance of all ions involved expresses transmemb electrical potential difference as weighted average of permeable ions' equilibrium potentials involved Gibbs - Donnan equilibrium steady-state properties of a mixture of permeant (e.g., initial KCl solution inside B) and impermeant ions (e.g., initial KY solution in side A, where Y is an anion to which the plasma membrane is completely impermeable) across a semi permeable membrane Under this condition, equilibrium between the A and B sides will be reached when the product of the concentration of the permeant cation K and the permeant anion Cl is equal in side A and side B. 16

17 Functions ( active transport ) Functions (Vmax concept ) 17

18 Functions e.g. ( pumps ) potential energy at the membrane level is associated with pumps e.g. electrical gradient e.g. conc. gradients e.g. action potential Functions e.g. ( calcium ) intracellular calcium is an important 2nd messenger e.g. release e.g. contraction e.g. communication 18

19 Functions e.g. ( sodium ) electrochemical and concentration gradients for sodium e.g. Na homeostasis e.g. absorption in gut e.g. renal absorption Functions e.g. ( organic solutes ) transmembrane Na as source of potential energy for work e.g. absorption of sugars e.g. absorption of amino acids e.g. Na / Ca and Na / H exchange 19

20 Functions e.g. ( water ) water goes where sodium goes e.g. absorption of water e.g. countercurrent mech. e.g. diuretics and alcohol Functions e.g. ( secretion ) glands secrete specific substances to the extra- cellular fluid (ECF) e.g. exocrine secretion e.g. endocrine secretion 20