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MEMBRANE PHYSIOLOGY. ARJUN MAITRA Asst. Professor Dept. of Physiology. LECTURE SLIDES FROM THE CLASSES TAKEN DURING 2008-09 SESSION. Topic: Cell membrane & Transport across the membrane Lecture taken for Courses: MBBS,BPT Useful for: B.ScNursing& others.

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slide1

MEMBRANE PHYSIOLOGY

ARJUN MAITRA

Asst. Professor

Dept. of Physiology

slide2

LECTURE SLIDES FROM THE CLASSES TAKEN DURING 2008-09 SESSION

Topic: Cell membrane & Transport across the membrane

Lecture taken for Courses: MBBS,BPT

Useful for: B.ScNursing& others

slide3

TO MY STUDENTS

HERE I HAVE TRIED TO SIMPLIFY THE HUGE SUBJECT WITH ANIMATIONS,

DIAGRAMS, FLOW CHARTS & RELEVENT MCQs.

DIFFERENT TEXT BOOKS AND REFERENCE BOOKS HAVE BEEN USED FOR

PREPARING THE CONTENTS.

REMEMBERTHESE SLIDES ARE NOT THE SUBSTITUTE OF YOUR TEXT BOOKS

ANIMATIONS AND DIAGRAMS ARE COLLECTED FROM DIFFERENT WEBSITE

SOLELY FOR EDUCATION PURPOSE.

what is a phospholipid
What is a Phospholipid?
  • It is a pair of fatty acid chains and a phosphate group attached to a glycerol backbone.
    • Polar (water-soluble) heads face out and the nonpolar fatty acids stay inside.

IN

OUT

slide12

cytoskeleton

cholesterol

carbohydrate

chains

membrane protein

outside the cell

interior of cell

slide19

Transport Proteins

  • Span the lipid bilayer
  • Interior is able to open to both sides
  • Change shape when they interact with
  • Solute
  • Play roles in active and passive transport
slide20

Carbohydrate layer (Glycocalyx) on the cell surface

Protecting the cell surface from mechanical and chemical damage

Lymphocyte stained with ruthenium red

solutions
Solutions
  • Solutions are made of solute and a solvent
  • Solvent - the liquid into which the solute is poured and dissolved. We will use water as our solvent today.
  • Solute - substance that is dissolved or put into the solvent. Salt and sucrose are solutes.
types of cellular transport

Weeee!!!

high

low

This is gonna be hard work!!

high

low

Types of Cellular Transport
  • Passive Transport

cell doesn’t use energy

    • Diffusion
    • Facilitated Diffusion
    • Osmosis
  • Active Transport

cell does use energy

    • Protein Pumps
    • Endocytosis
    • Exocytosis
slide25

Diffusion

Diffusion: random movement of particles from an area of high concentration to an area of low concentration.

(High to Low

slide26

Fick's law of diffusion

J = - DA(DC/DX)

where

J is the net rate of diffusion,

D is the diffusion coefficient, D = - ½b2f

A is the area, and Δc/Δx is the concentration gradient.

The minus sign indicates the direction of diffusion.

TYPICAL VALUES OF THE DIFFUSION COEFFICIENT

slide27

Principles of Diffusion

• Diffusion is the random mixing of particles that occurs

in a solution as a result of the kinetic energy of the

particles.

• Diffusion rate across plasma membranes is influenced

by several factors:

– Steepness of the concentration gradient

– Temperature

– Size or mass of the diffusing substance

– Surface area

– Diffusion distance

slide28

FacilitatedDiffusion

diffusion of specific particles through transport proteins found in the membrane

slide29

Conformational change of a carrier protein

Mediates passive transport

Change is spontaneous and random, so dependent on concentration

slide32

Permeability of plasma membrane

General principles II

Permeability coefficient (cm/sec)

slide33

Osmosis: diffusion of water through a selectively permeable membrane

  • Water moves from high to low concentrations
active transport
Active Transport
  • celluses energy
  • actively moves molecules to where they are needed
  • Movementfrom an area of low concentration to an area of high concentration
  • (Low  High)
slide35

ACTIVE TRANSPORT

PRIMARY ACTIVE TRANSPORT SECONDARY ACTIVE TRANSPORT

slide36

3 ways of driving active transportation utilizing passive carriers

  • Coupled carriers
  • ATP-driven pumps
  • Light-driven pumps
slide38
Active transport enzymes couple net solute movement across a membrane to ATP hydrolysis.

An active transport pump may be a uniporter or antiporter.

slide39
ATP-dependent ion pumps are grouped into classes based on transport mechanism, as well as genetic & structural homology.

Examples include:

  • P-class pumps
  • F-class (e.g., F1Fo-ATPase to be discussed later) & related V-class pumps.

ABC (ATP binding cassette) transporters, which catalyze transmembrane movements of various organic compounds including amphipathic lipids and drugs, will not be discussed here.

slide40
P-class ion pumpsare a gene family exhibiting sequence homology. They include:
  • Na+,K+-ATPase, in plasma membranes of most animal cells is an antiport pump.

It catalyzes ATP-dependent transport of Na+ out of a cell in exchange for K+ entering.

  • (H+, K+)-ATPase, involved in acid secretion in the stomach is an antiport pump.

It catalyzes transport of H+ out of the gastric parietal cell (toward the stomach lumen) in exchange for K+ entering the cell.

slide41
P-class pumps (cont):
  • Ca++-ATPases, in endoplasmic reticulum (ER) and plasma membranes, catalyze ATP-dependent transport of Ca++ away from the cytosol, into the ER lumen or out of the cell.

Some evidence indicates that these pumps are antiporters, transporting protons in the opposite direction.

Ca++-ATPase pumps function to keep cytosolic Ca++ low, allowing Ca++ to serve as a signal.

slide42

Na+-K+ Pump, ATPase

P-type transport ATPase (dependent on phosphorylation)

slide43

Molecular weight

Alpha Subunit 100,000

Beta Subunit 55,000

b

  • Alpha Sub unit
  • Span cell membrane for 10 times
  • NH2 and COOH both terminal
  • Intracellular
  • Phosphorylation site Asp 376
  • Heterogenicity exists
  • Three isoforms are
  • a1 ----- membrane
  • a2--- muscle,heart,adipose tissue,brain
  • a3---- heart, brain

a

slide44

Beta Subunits

  • Single membrane spanning unit
  • 3 extracellular glycolisation sites
  • Heterogenicity exists
  • 3 iso forms
  • b1---absent in astrocytes,vestibular cells, glycolytic fast twich muscles
  • b2 ---fast twich muscles
  • Beta 3 ----- not reported
slide47

EXOCYTOSIS

  • TWO PATHWAYS:
  • NONCONSTITUTIVE PATHWAY (SLOW)
  • CONSTITUTIVE PATHWAY (RAPID)
slide49

KISS AND RUN DISCHARGE

  • SNARE = SYNAPTOSOMAL ASSOCIATED RECEPTOR
  • FOR EXOCYTOSIS(soluble NSF attachment
  • receptor)
  • t-snare & v-snare

NSF =N-ethylmaleimide-sensitive factor

SNAP = soluble NSF attatchment protein

slide51

ENDOCYTOSIS

  • TWO TYPES
  • CLATHRIN MEDIATED
  • CONSTITUTIVE
role of ions
Role of Ions

+

SODIUM Na

+

POTASSIUM K

_

CHLORIDE Cl

+ +

CALCIUM Ca

-

A

slide60

Nernst Equation & Equilibrium Potential

  • ELECTRICAL DRIVING FORCE = CHEMICAL DRIVING FORCE

EK = -75mV

(Nernst Potential)

role of ions1
Role of Ions

+

SODIUM Na

+

POTASSIUM K

_

CHLORIDE Cl

+ +

CALCIUM Ca

-

A

slide62

GOLDMAN’S EQUATION

A new approach to quantify the contribution of different ions

  • Concentration gradient
  • Conductance/Permeability

PERMEABILITY RATIO (At Rest) PK : P Na : P Cl = 1.0: 0.04 : 0.45

(At peak of Action Potential) PK : P Na : P Cl = 1.0 : 20 : 0.45

voltage gated potassium channel
Voltage Gated Potassium Channel

Voltage gated Slow

Voltage Gated Fast

Inward Rectifier Channel

slide66

CELLULAR COMMUNICATION

  • INTERCELLULAR INTRACELLULAR
  • NEURAL
  • ENDOCRINE
  • PARACRINE
  • AUTOCRINE
slide67

INTRACELLULAR COMMUNICATION

CONCEPT OF FIRST & SECOND MESSENGER SYSTEM

  • LIGAND AND RECEPTOR

LIGAND

RECEPTOR

slide68

FIRST MESSENGERS ARE THE EXTRA CELLULAR LIGAND

SECOND MESSENGERS ARE INTRACELLULAR MEDIATORS

  • HOW DO THE SECOND MESSENGERS WORK?
  • BY ALTERING THE ENZYME ACTIVITY
  • TRIGGERING EXOCYTOSIS
  • BY ALTERING GENE TRANSCRIPTION
  • COMMOMNLY OCCURING SECOND MESSENGERS
  • cAMP
  • cGMP
  • CALCIUM
  • IP3
  • TYROSINE KINASE
  • PHOSPHO PROTEIN PHOSPHATASE
slide69

HOW THE MESSEGE IS TRANSFERRED

FROM FIRST MESSENGER TO THE SECOND MESSENGER

?

MESSENGER / LIGAND

2ND MESSENGER

EFFECT

slide70

G Proteins

TRANSLATE A SIGNAL

TO A BIOLOGICAL EFFECT

SMALL G PROTEINS

HETEROTRIMERIC G PROTEIN

 G proteins were discovered by Alfred G. Gilman and Martin Rodbell

For this discovery they won the 1994 Nobel Prize in Physiology or Medicine.

slide71

HETEROTRIMERIC G PROTEINS

3 SUBUNITS

a,b,g

Alpha bound to GDP

bg acts as activator

Alpha has intrinsic

GTPase activity