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Membranes

Structure of biological membranes Function of biological membranes Examples of biological 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:!

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.

Topic #! Topic lecture! Silverthorn!

Week 1 to week 2! Topic #1! Introduction (pre-requisite material)! 1 - 5! Pre-requisite!Material!(chapter # 5)!!!lectures, recitations, office hours, review, exam1 !(chapter # 8)!

Topic #2! Membranes (pre-requisite material)!!

1 - 5!

Topic #3! Homeostasis and Signal Transduction! 6!

Topic #4! Endocrine Communication and the Endocrine System! 7!

Topic #5! Neural Communication and the Sensory System! 8 - 11!

Topic #6! Muscle, Muscle Contraction and their Regulation! 12 - 13!

REVIEW #1 material from topic #01 – #06 !EXAM #1 material from topic #01 – #06 (33%)!!

1 - 13!1 - 13!

Week 3 to week 4! Topic #7! Basic Physiology of the Cardiovascular System! 14 - 17! lectures, recitations, review, exam2!(chapter # 7) !

Topic #8! Basic Physiology of the Respiratory System! 18!

Topic #9! Basic Physiology of the Renal System! 19 - 20!

REVIEW #2 material from topic #01 – #09 !EXAM #2 material from topic #01 – #09 (33%)!!

1 - 20!1 - 20!

Week 5 to week 6! Topic #10! Basic Physiology of the Gastrointestinal System! 21 ! lectures, recitations, review, exam3!(chapter # 6)!

Topic #11! Food Intake, Metabolism, Energy Balance and Exercise! 23 - 25!

Topic #12! From Sexual Differentiation to Adult Reproduction! 26!

REVIEW #3 material from topic #01 – #12 !EXAM #3 material from topic #01 – #12 (33%)!!

1 - 26!1 - 26!!

Course Outline

(all tests are cumulative)

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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”)

(membranes are phospholipids bilayes interspersed with proteins)

Functions of Cell Membranes

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Membranes (“structure”)

(membranes are phospholipids bilayes interspersed with proteins)

Membranes (“structure”) !membranes are phospholipid bilayers interspersed with!

•  associated proteins having trans-membrane 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)

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Membranes (“structure”)

(membranes are phospholipids bilayes interspersed with proteins)

Membranes (“structure”)

(membranes are phospholipids bilayes interspersed with proteins)

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Membranes (“structure”)

(membranes are phospholipids bilayes interspersed with proteins)

Membranes (“structure”)

(membranes are phospholipids bilayes interspersed with proteins)

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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)

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Membranes (“proteins”)

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

Membranes (“channels”)

some proteins are ion channels !

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“channels”)

some proteins !are ion channels !

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

Membranes (“transporters”)

some proteins !are transporters !

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“transporters”)

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

Membranes (“structure”)

some proteins are !- ion channels!- transporters !

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“receptors”) •  membranes are phospholipid

bilayers interspersed with!•  associated proteins having trans-

membrane 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)!

plasma memb.

COOH

2 ECF

ICF

seven - transmembrane domain receptors

ß - adrenergic and glucagon receptors among many others

N H

G

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

Membranes (“receptors”)

other proteins are receptors !

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“receptors”)

EGF insulin PDGF ANP

GH, Prl, cytokines

kinase

Cys rich

Cys residues

JAK2

ECF

ICF

COOH

N H2

hydrophobic aa

single - tm domain receptors

other proteins !are enzymes !and / or receptors!

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

Membranes (“functions”)

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“functions”)

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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.

!!!(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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Membranes (“functions”)

(some proteins are ion channels, some are transporters, some are enzymes, some are receptors)

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”)

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)!

!Diffusion!

!

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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

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Functions (“facilitated diffusion”)

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!

(e.g. Ca)!

(e.g. Glucose)!

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.!

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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, !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 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. !!

(important concepts for later lectures)

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Functions (“active transport”)

Functions (Vmax concept”)

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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!

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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!

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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!