ch 5: membrane dynamics - las positas...
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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:
– Excretion
–Metabolism (production of metabolites)
• Liver is major organ for clearance
• Other ways to clear molecules: Kidneys, saliva, sweat, breast milk, hair, lungs
Fig 5-2
Homeostasis
• Body’s ability to maintain relatively stable internal environment (dynamic steady state!)
• H2O 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
• Diffusion rate to membrane surface area
1
Thickness of membrane
Fick’s law of Diffusion
surface x conc. X membranearea gradient permeability
membrane thickness
Diffusion
rate
Fig 5-6
Protein Mediated Transport
For all lipophobic molecules
Two mediated transport categories: 1. Passive transport (facilitated diffusion)
2. Active transport
Two categories of transporter proteins1. 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
Have gates, but gates are open most of the time.
Also referred to as “leak channels”.
Gates closed most of the time
Chemically gated channels (controlled by messenger molecule or ligand)
Voltage gated channels (controlled by electrical state of cell)
Mechanically gated channels (controlled by physical state of cell: temp.; stretching of cell membrane etc.)
Carrier Proteins (2nd type of transport protein)
• 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)
Compare to Fig 5-13
Uniport vs. Cotransport
SymportMolecules are
carried in same
direction
Examples:
Glucose
and Na+
AntiportMolecules 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 laterFig 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
1o 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
ECF: high
[Na+], low [K+]ICF: high [K+],
low [Na+]
Fig 5-17Fig 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 symporterother examples
• 2 mechanisms for Glucose transport
Fig 5-18
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
– Potocytosis via caveolaeFig 5-24
Exocytosis
Intracellular vesicle fuses with membrane
Requires energy and Ca2+
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 membraneNa+/K+-ATPase only on basolateral membrane
Fig 5-26
Transcytosis
• Endocytosis vesicular transport exocytosis
• Moves large proteins intact
• Examples: – Absorption of maternal
antibodies frombreast milk
– Movement of proteins across capillary endothelium
OsmosisMovement of water down its concentration
gradient.
Osmotic
pressure
Opposes
movement
of water
across
membrane
Water moves freely in body until osmotic
equilibrium is reached
Compare to Fig. 5-29
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 OsM
Why?
Osmolarity takes into account the
dissociation of molecules in solution
Convert Molarity to Osmolarity
Osmolarity = # of particles / L of solution
• 1 M glucose = ? OsM glucose
• 1 M NaCl = ? OsM NaCl
• 1 M MgCl2 = ? OsM MgCl2
• Osmolarity of human body ~ 300 mOsM
• 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, NaCl*)
• 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
• Membrane potential = unequal distribution of charges across cell membrane
Fig 5-32
• 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 mV)
• Measuring membrane potential differences
Resting Membrane Potential Difference
Fig 5-33
Resting Membrane Potential Mostly Due to Potassium
Cell membrane – impermeable to Na+, Cl - & Pr –
–permeable to K+
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 mVFig 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 mV Fig 5-35
Resting Membrane Potential
Reasons:• Membrane permeability: K+
> Na+ at rest
• Small amount of Na+ leaks into cell
• Na+/K+-ATPase pumps out 3 Na+ for 2 K+
pumped into cell
In most cells between -50 and -
90 mV (average ~ -70 mV)
Stimulus
Depolarization
Repolarization
Hyperpolarization
Changes in Ion Permeability
• lead to change in membrane potential
• Terminology:
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 Ca2+ channel
– ATP-gated K+ channel
Fig 5-38
Cells Avoid Reaching Glucose
Equilibrium
???
Running problem:
Cystic Fibrosis
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