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1.Cell1.Cell HomeostasisHomeostasis
Body FluidBody Fluid CompartmentsCompartments
1.11.1 CellCell MembraneMembrane
((structurestructure,, functionsfunctions ,, actionaction
potentialpotential ))
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Human Body structure
Cell
tissue
organ
system
HUMAN BODY
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Coordination of Systems and Organs
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Claude Bernard(1813-1878)
La fixit du milieu intrieur est
la condition de la vie libre.
The fixity of the internal
environment is the
condition for free life.
Homeostasis
WalterCannon(1929)
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HOMEOSTASIS Cannon W.B., 1939
-all mechanisms through which bodily equilibrium is
maintained ( body fluid composition, temperature, blood pressure, blood
glucose level)
INTERNAL MILIEU Claude Bernard-,, all around ,, cells
- offers nutritives substances
- realises elimination of metabolites
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The cell : morpho functional unit of human body.
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Cell Membrane
- separates / unites two compartments with different composition
- intracellular space (compartment , environment)- extracellular space ( compartment )
Na+
K+
Cl-
Proteins
Glucose
Osmolarity
extracelular
142 mM/L
4.4 mM/L102 mM/L
7 g/dL
5.5 mM/L
291
intracelular
15 mM/L
120 mM/L20 mM/L
30 g/dL
-
290
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Cell membrane
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Transport
Enzymatic activity
Sending informations
Intercellular comunications
Intercellular recognition
Attachment to cytoskeleton
Functions of the cell membrane :
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Hystory :
Overton (1895): if a substance is
more lipo-soluble , it has a better
permeability through the membrane- conclusions regarding the lipid
profile of the cell membrane .
Davson and Danielli (1935) they
introduce the concept of a protein
structure for the cell membrane .
Singer & Nicholson (1972)- they
offer the model of ,,fluid mosaic,,-
phospholipids and cholesterol form
a a fluid lipid bilayer where
proteins can move free. In
conclusion cell membrane is a
dynamic structure with specificcharacteristics in order to
accomplish various functions.
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The cell membrane is a lipid bilayer semipermeable structure
allowing the passage only for some molecules .
- no H2O, ions, hidrophyle molecules.
- yes - gas, hidrophobe substances .
Membrane proteines allow transport for H2O, ions and hidrophyle
molecules .
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CELL MEMBRANE lipids
proteins
glucides
MEMBRANE LIPIDS: -phospho-lipids
-cholesterol
-phospholipids - contain fat acids - C chain, (carboxil group terminal)
- particular characteristics:
- hidrophyle part ( C chain)
- hidrophobe part ( carboxil group )
- lipid bilayer
- hidrophobe head (inside )
- hidrophyle head (outside)
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MEMBRANE PROTEINS
A. INTEGRAL PROTEINS
- connected with hidrophobe layer of the
membrane .
1.transmembrane proteins: cross lipidic bilayer
- channels:
- pomps:
- pores-receptors:
2.proteins expressed only on one face of the membrane
B. PERIPHERAL MEMBRANE PROTEINS
- connected with hidrophyle part of the lipidic layer or with integral proteins- cytoskeleton - role in membrane rigidity
- glicocalix -role n intercellular atachment
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MEMBRANE PROTEINS
A. INTEGRAL PROTEINS - c o n nec te d w it h h id ro p ho b e la y er o f the m embrane .
1.transm embra ne proteins: cross l ipidic bi layer - channels: allows the passage only for substances with small molecule with
electric charge
- gates acctive or innactive - selectivity
- pomps: - pores -receptors:
2.p ro t ei ns ex p r es se d o n ly o n o n e fa c e o f t he m e m b ra n e
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MEMBRANE PROTEINS
A. INTEGRAL PROTEINS - c o n nec te d w it h h id ro p ho b e la y er o f t h e membrane .
1.transm embra ne proteins: cross l ipidicbilayer
- channels: - pomps: - pores - channels without gates , allways
open.
- ex. aquaporines ( allow thepassage for water renal colector tube)
-receptors:
2.p ro teins ex p res se d o nl y o n o n e fa c e of t he m e m b ra n e
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MEMBRANE PROTEINS
A. INTEGRAL PROTEINS - connected with hidrophobe layer of the membrane .
1.transmemb rane proteins: cross lipidic bilayer - channels: - pomps: allow ions transfer against concentrationgradient or voltage gradient. - pores: - receptors:
2.proteins expressed on ly on one face of the membrane
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MEMBRANE PROTEINS
A. INTEGRAL PROTEINS - c on n ecte d w ith h id ro pho be la y er o f t he m e m b ra n e .
1.transm embrane proteins: cross lipidic bi layer - channels: - pomps: - pores
-receptors:
2.p ro t ei ns e x pr es se d o n ly o n o n e fa c e o f t h e m e m b ra n e
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MembraneMembrane ReceptorsReceptors
areare proteinprotein moleculesmolecules thatthat reactreact withwith ligandsligands inducinginducing specialspecial reactionsreactions
insideinside thethe cellscells.. TheThe mostmost importantimportant receptorsreceptors areare classifiedclassified asas adrenergicadrenergic andand
cholinergiccholinergic
1.1. AdrenergicAdrenergic receptorsreceptors are of 2are of 2 typestypes ALPHAALPHA andand BETABETA ..TheyThey reactreact toto
sympatheticsympathetic neurotransmitterneurotransmitter-- norepinephrinenorepinephrine ..
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The actions of norepinephrine depend on the type of receptorsactivated :
Alpha 1 receptors - contraction of smooth muscles in vessels andbronchioles
Alpha 2 receptors - contraction of smooth muscles of digestive sphincters. Beta 1 receptors - excitatory effects on heart . Beta 2 receptors - relaxation of smooth muscle in bronchioles and
muscular vessels.
2. Cholinergic receptors are of 2 types nicotinic and muscarinic. Theyreact especially to acetylcholine
NicotinicNicotinic receptorsreceptors areare stimulatedstimulated byby acetylcholineacetylcholine andand nicotine.nicotine. TheyTheyareare foundfound inin allall ganglionicganglionic synapsessynapses andand neuromuscularneuromuscularjunctionsjunctions wherewhereareare blockedblocked byby curaracurara..
..MuscarinicMuscarinic receptorsreceptors areare stimulatedstimulated byby acetylcholineacetylcholine andand muscarine.muscarine.TheyThey areare foundfound atat targettarget organsorgans whenwhen acetylcholineacetylcholine isis releasedreleased byby postpost--ganglionicganglionic neuronsneurons ((parasympatheticparasympathetic)).. TheyThey areare blockedblocked byby atropine.atropine.
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EnzimesEnzimes
-- ProteinsProteins thatthat playplay
importantimportant rolesroles ininproteinprotein synthesissynthesis
insideinside thethe cellscells
-- adenylateadenylate cyclasecyclase
-- guanilateguanilate cyclasecyclase
-- phospholipasephospholipase CC
-- proteinprotein kinaseskinases A, CA, C
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SSecondecond MMessengersessengers -- substancessubstances insideinside thethe cellscells thatthat mediatemediate thetheactionaction ofofligandsligands actingacting onon thethe cellscells
cAMPcAMP
cGMPcGMP
IP3IP3
DiacylDiacyl--glicerolglicerol
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The skeleton maintains the shape of the cells ( during cell
divisions), realises some selective movements or activities of
intercellular transport ( vesicles )
PERIPHERAL PROTEINS
-CYTOSKELETON-
PERIPHERAL PROTEINSPERIPHERAL PROTEINS
--CYTOSKELETONCYTOSKELETON--
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CYTOSKELETONCCYTOSKELETONYTOSKELETON
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- Using as a criterium the dimensions of transported molecules:
- microtransfer system
- macrotransfer system
1. Microtransfer system
PASSIVE TRANSPORT- transport according the concentration gradients of
substances
- without energy consumer
ACTIVE TRANSPORT
-against gradients
- with energy consumer
Transport of substances across the cell membrane
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1. PASSIVE
TRANSPORT
1 .1.DIFFUSION :
-3 types :
- simple diffusion .
- diffusion facilitated
by carrier protein
- diffusion using
channel proteins
1.2. OSMOSIS
Transport of substances across the cell membrane
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1.1.1 .Simple Diffusion- without energy consumer- takes place until all concentrations are equal.
-substance flow depends of :- concentrations difference ( D )
-membrane permeability ( P ) Fick low : Flow D x P x S- surface ( S)
- liposoluble substances cross the membrane dissolving in lipidic bilayer
(O2, CO2)- Hidrosoluble substances cross membranes using membrane proteins (
channels )
1. PASSIVE TRANSPORT
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Simple Diffusion
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1.1.2. Diffusion facilitated by
carrier protein
- Selectivity
- Specificity
- Saturation
- takes place according gradients .
- with superior speed and debit than
concentrations difference
- uses a carrier protein
- without energy consumer
- stops when concentrations become equal.
- limitated by a maximum capacity of transport
imitat induced by the saturation of the
transporter ( ex. glucose )- low transport capacity in comparation with ions
channels (102-103 molecules/sec)
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1.1.3.Diffusion using channel
proteins
- for particles with electric charge.
- takes place according gradients .
- with superior speed and debit than
concentrations difference
without energy consumer
- stops when concentrations become equal.
Ions channels :
- High selectivity for only one ion- With permeability modulation of the
channel ( ex.- membrane potential )
A
B
A = poarta activare
(deschis de depolarizare)
B = poarta inactivare
(nchis de depolarizare)
Na channel
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1.2. OSMOSIS-Mechanism of passive transport
-Allows passage of water from a compartment with lower concentrations ina compartment with higher concentration
Osmotic pressure - a force used to stop the movement of water through a
membrane which separate a solution from pure water.
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2. ACTIVE TRANSPORT
- against gradients- with energy consumer
2. 1. PRIMARY ACTIVE TRANSPORT
2.2. SECONDARY ACTIVE TRANSPORT
Transport of substances across the cell membrane
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2. 1. PRIMARY ACTIVE TRANSPORT
- uses a system directed coupled with an energy reactions .
- ionic pumps
- energy source = ATP ( synthesized by mithocondrion )
- ATP -- ADP + P (ATP-ase)
- ATP-ase Na/K or Na pump - in almost cell membranes. ( role in
maintenance of high concentration of K inside the cell - maintenance of
membrane potential )
- inhibited by medicines - digitala, ouabaina
2. ACTIVE TRANSPORT
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Ca2+
H+
Ca ATP-ase4 Muscle cell .4 Endoplasmic reticulum .
H+ ATP- ase4 renal tubular cells acidification ofurine .
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2.2. SECONDARY ACTIVE TRANSPORT
4 the primary active transport generate chemical gradients or electricalgradients which represent ,,forces used to transfer of other substancesusing a common transporter.
4 simport co-transport ( glucose )4 antiport contra- transport ( Na-K )
INT
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4CYTOSIS- Transport of big particles across cell
membrane - 5-400 nm.- Specific for macromolecules:
- proteins- lipoproteins
- polizaharides
Endocytosis vesicles are incorporatedin cells by invagination , using ATP.
phagocytosis for solid particles- pinocytosis for liquid particles
Exocytosis vesicles are eliminated from
the membrane .
Trancytosis - macromolecules cross cellmembrane .
- macrotransfer system-
Transport of substances across the cell membrane
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MEMBRANEMEMBRANEPOTENTIALPOTENTIAL
-- BecauseBecause ofofthethe selectiveselective
permeabilitypermeability ofofcellcell membrane,membrane,therethere isis aa differentiateddifferentiated repartitionrepartition
ofof ionsions insideinside andand outsideoutside ofofthethe
cellcell..
-- InsideInside predominatepredominate potassiumpotassium
ionsions,,whilewhile outsideoutside predominatepredominate
sodiumsodium ionsions,, thethe interior ofinterior ofthethe
cellcell beingbeing more negative asmore negative ascomparedcompared withwith thethe exterior.exterior.
TheThe differencedifference ofof electricalelectrical chargescharges createscreates aa membranemembrane potentialpotential ofof--7070mVmV at rest (at rest (restinrestingg potentialpotential).).
PotassiumPotassium ionsions havehave aa tendencytendency toto leakleak outout byby facilitatedfacilitated diffusiondiffusion throughthroughchannelchannel proteinsproteins.. MostMost ofofsodiumsodium channelschannels areare gatedgated andand remainedremainedclosedvclosedv keepingkeeping thethe concentrationconcentration outsideoutside highhigh..
TheThe differencedifference isis maintainedmaintained byby thethe active transport ofactive transport ofionsions acrossacross thethemembranemembrane byby thethe sodiumsodium--potassiumpotassium pumppump ..
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WhenWhen thethe cellcell receivesreceives aasignal,signal, likelike aa voltagevoltagevariationvariation,,thethe permeabilitypermeability ofof
thethe membranemembrane changeschangesbecausebecause voltagevoltage gatedgatedsodiumsodium channelschannels openopen andandsodiumsodium flowsflows inwardinward..
TheThe insideinside ofofthethe cellcell brieflybrieflybecomesbecomes moremore positivepositive thanthanoutsideoutside..
The abruptThe abrupt modificationmodification ofofthethe polaritypolarity,, withwith aadepolarisingdepolarising andand aarepolarisingrepolarising phasephase,,constitutesconstitutes thethe actionactionpotentialpotential..
WhenWhen thethe depolarizationdepolarization isisendedended thethe sodiumsodium channelschannelscloseclose andand potassiumpotassium
channelschannels open.open. FinallyFinally,, thethe sodiumsodium --
potassiumpotassium pumppump becomesbecomesoperationaloperational andand restoresrestores thetherestingresting potentialpotential ..
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ActionAction PotentialPotential
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TheThe restingresting andand actionaction potentialspotentials cancan bebe measuredmeasured usingusing intracellularintracellularmicroelectrodesmicroelectrodes , made of, made ofthinthin glassglass tubestubes withwith aa sharpsharp tip,tip, filledfilled withwith
potassiumpotassium chloridechloride..
TheThe microelectrodesmicroelectrodes cancan bebe introducedintroduced inin thethe cellcell withoutwithout thethedestructiondestruction ofof thethe membranemembrane andand thethe differencedifference ofof electricalelectrical potentialpotentialisis recordedrecorded onon oscilloscopeoscilloscope..