Chapter 1:

- Why does the cell act as permeability barrier? How is it able to maintain
differences in salt concentrations among membranes while still maintaining
homeostasis?
- Force of friction is neglected and we will focus on the first 2 forces
- To measure the voltage we use a voltmeter or an electrometer. The
voltmeter has a + lead inside the cell and a _ lead outside the cell.
- So Vm is V inside -V outside
- Voltage gradiant: diff in voltage . from the graph we knew that the voltage
gradiant exists in the membrane only
- Gradiant is always directed from low to high value
- Inside the cell in neg and outside is positive so the voltage inside the cell is
always lower fro outside so the gradiant is always from inside to outside
yeene mn low la high
- Positive ions like Na+ are attracted to inside the cell and negative ions like
chloride are attracted to the outside so Fna= -(+) dv/dt meaning that this
force moves sodium inside the cell \. Chloride Fe= +dv/dt yeene F and
voltage grad have same direction
- Brownianan motion is called the thermal energy of the system solutes-
solvant.
- Any gradiant is directed from low to high
- The fick eq is used to determine how many mm entered the cell
- The net flux is the sum of an influx and outflux or efflux and these are called
unidirectional fluxes
- Phi o-I yeene out to in yeene influx
- Both influx and efflux are expressed by mol/sec and influx has – direction
- D is the slope of the line and this D is specific to each solute and D is
calculated not measured
- Fick eq applies to charges or polar molecule like glucose and it only gives
the net flux due to force of diffusion bass kmn fi electrical force Fe bass not
determined by fick eq
- At normal conditions Na moves inwards and potassium outwards
- Fe is due to voltage gradiant w Fd is due to concentration grad
- KT is the kinetic energy of the molecul
 - The laarger the molecule the more time it takes to diffuse
- Cell membranes evolved transporters for molecules to reach tissues faster
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- Transmembrane transport part 2:

- Semipermeable membrane is permeable to water not solutes

- Water will move from higher water concentration to lower water conc
- osmotoic pressure and osmosis are used interchangeably
- osmotic pressure is the pressure we should exist to prevent water from
entering from B to A through an ideal semipermeable membrane
- pressure coming from the solution in B on A is called hydrostatic pressure
and once Ph = Po no net flow of water will occur
- water mmoves from right to left yeene from where water conc is higher to
lower so a certain column of water will be present in the left side exerting
hydrostatic pressure equal to Po left-Po right
- we can convert this height into osmotic pressure using P= rho.g.h which we
can also convert to ideal gaz law P=nRT/V and n/V is concentration so P=
CRT
- homeostasis yeene intracellular Po= extracellular osmotic pressure
- colligative property of a solute depends only 3a its concentration msh type
or nature
- osmotic coefficient phi deiffers among solutes cz it is specific
- fi theroretical and behavioral aw physical behavior of a solution so like NaCl
is diff than calculating the osmotic pressure on paper
- we can lower the freezing point of water by adding solutes metl l salt bil
shete
- osmolarity and tonicity: A and C are isoocmotic yeene same osmot
ic pressure. A and C are hyperosmotic compared to B
water permeability of a cell is the most imp slide: in steady state aw homeostatsis
our intracellular osmolarity = extracellular osmolarity but sodium outise is like 150
mmol and Na+ is 5 inside so it diffuses taking water with it. Bass the intracellular
volume is constant so kif hek?
Cell membranes have aquaporins aw water channels so they allow passage of
water.
Osmolarity is by phi x Ix C ---- solution inside or outside of the cell
Tonicity yeene behavior of the cell ---what happens to the volume if the cell is
placed in solution
Eza bil solution dal l volume the same yeene isotonic solution
Can we calculate the volume of water flown via osmosis in microliter/sec
Delta pi is the diff in osmolarity between 2 solutions separated by semipermeable
membrane
Mn ideal la physiological settings we use sigma aw reflection coefficient
Eza 3enna 2 solutions wehde 0.5 w wehde 1 l water 7a trouh mn 0.5 la 1 bass
solutes kamen will move from 1 to 0.5 by diffusion w nehna mna3ref enno when
solutes move byekhdo water ma3on so in reality we have to examine adde l
membrane allows solutes to diffuse
Sigma is zero yeene Vw is zero yeene no osmotic water flow
The larger the molecule the larger sigma the larger water flow by osmosis

- Part 3:
- To see how a substance moves along the membrane lezim nshouf its type if
polar aw nonpolar
- Simple diff yeene molecules move from high to low conc + nature of solutes
allows them to move yeene nonpolar like NO
- Carrier proteins are for aa to pass
- Saturation= ligand and binding site on the carrier protein so the flow
becomes constant in the graph
- We will not calculate bass shoufe kif l relation
- At S=Km , V=Vmax
- Take home message: diffusion---no saturation behavior bass bil protein
mediated kinetics fi saturation behavior
- Although ion channels are proteins, they do not saturate
- Glucose transporters, gluc is polar that will be transported using SGLT1 and
glc should be in D stereospecificity not S
- Phloretin is not a carbohydrate and when present at a certain conc it
inhibits glc transport to RBCs
- Active/fac: lets say fi glc higher outside than inside diffusion law bet2oul
enno lezim yrouh mn out la in bass glc is polar so it needs carrier proteins
transporters. Energy must be spent and this energy is Brownian motion
=thermal energy of the system
- Lal active: fi motion mn low la high conc and tis mvt baddo energy coming
from ATP
- Facilitated hiye l passive bil nesbe lal ATP
- Na/K pump pumps 3 Na from in to out and always 2 K from out to in so
vectorial transport yeene always has 1 direction
- For primary active transport to occur fi a cycle of phosphorylation and
dephosphorylation of the transporter protein. Phosphorylation triggers a
covalent regulation of the protein
- Sodium potassium pump is a primary active transporter and an enzyme by
itself
- Sodium binds the intracellular site w fi 3 binding sites msh 1
- Glucose enters the membrane using the gradiant of sodium driven by Fd
and Fe inward so Fnet is inside pushing glucose ma3a. what maintains this
force la jowa is the sod potassium pump which transports 3 sod in to out
insuring the energy from sodium electrochemical gradiant to transport
glucose
- Sodium potassium pump is an example of ion exchange atpases causes it
uses atp to drive ions
- Apical side---lumen while basolateral----blood
- SGLT is an exp of sec active transport and exits by facilitated diff through
Glut 2
- Aquaporins allow the passage of water in or out depending on the osmotic
gradiant so unidirectional
- Osmotic pressure in lezim tkoun = out
- They have 3 extracellular loops w 2 intracellular ones
- Lezim ykoun 3ndn asp lys his
- Know that NPA motif is characteristic of aquaporin motifs and 1 single
functional aquaporin is an assemlbly of 4 homologous domains yeene
tetramer of the unidimensional seq in the slide
- In case of aa deletion aw addition fi ysir fi increase aw decrease in
aquaporins to protein. Overexpressed= water is rleelreased leading to
dehydration masalan

Chap 3: The gibbs donnan equilibrium

- In the fig la weh 7a trouh Na+ b awal fig? it will go towards B under the
effect of diffusion + under the effect of electric force cz + betrouh 3nd _ due
to attraction So in 1 sodium net flow is from A to B. Now in 2 Fe and Fd are
opposite to each others So sodium moves hasab l force l a2wa
- muE is in volts msh millivolts ntebhe
- Delta mu hiye muA -MuB yeene eza negative betkoun B akbar w eza + A
akbar
- The term spontaneous or passive flow refers to-------NO ATP HYDROLYSIS
- At electrochem eq no net flow of the ion will take place from one side to
the other so no specific direction to determine
- Use nernst eq bil ahmar yeene ma3 –
- Derivation msh matloube
- Exp 1 answer should be: if K+ is at electrochemical eq between A and B it
should satisfy the Nernst equation
-
- Part 2:
- The cytosol contains ions for which the membrane is permeable and others
not.
- Impermeant molecules such as nucleic acids, proteins and polyphosphates
- Driven by Brownian motion and due to diffusion chloride will move from B
to A. In A sar fi additional – charge mn B so sar fi electrical potential
difference so the flow of an ion through the membrane is enough to trigger
potential diff across the membrane
- K+ will be driven by Fe from B to A so the electric potential diff that was
triggered by chloride moving from B to A is the driving force for K+ from B
to A bass until when? K and Cl will come into electrocch eq yeene each ion
will satisfy Nernst eq
- Ente use l eq bil ahmar w li abla bass fehem kif ejet
- Everytime fi monovalent ions in solution, 2 ions in eq satisfy donnan eq
- The question now is how much chloride must flow from B to A to attain
donnan eq ? howe lezim cl moves add K+however in reality K+ ions flowing
from A to B is larger than Cl so we assume z as nb of K ions and Cl ions
moving from B to A
- X- is put zero laino mna3ref enna impermeant ion
- Fig slide: we will see a higher concentration of ions in A than in B this
means enno osmotic pressure bil A akbar mn B
- Ea-Eb= -18 in either case K aw Cl are in eq and since each of these are at eq
yeene this is donnan eq in which the presence of an immobile ion will
influence ionic distru=ibution of permeant ions
- Slide osmotic imbalance: osmotic P of A is larger than B so water goes from
A to B until osmolarity in both is equal so each ion will enter a new cycle of
Gipps donnan eq. all water from side B will end in A if water stop moving
from b to a.
- Ma fina to have donnan eq bil human body so animals evolved primary
active transport like sod potassium pump kermel tdal l osmolarity of
intracellular and extracellular milieu equal
- So l dug li mnekheda lezim tkoun isotonic
- osmotic imbalance yeene Posm cytosol akbar mn P osm lal extracellular
milieu---- cells swell and burst
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-
- RMP
- To talk about steady state lezim osmolarity inside equal osmolarity outside
yeene homeostasis
- Na K pump take sodium out to maintain constant concentration in/out so
Na outside will always be higher and this is steady state
- Na will be actively driven out yeene using 1 ATP. What goes in must go out.
- I have 3 sodium going in and 3 out ----- phi net is zero so I is zero from the
equation so because what goes in must go out we can use the term flow
and current interchangeably
- Concentration cell model yeene I designed a membrane that allows only
specific molecules to pass by masaln permeable to potassium not to
chloride. At time zero fi diff in concentration of K and it flows between A
and B it will establish and electric potential diff across the membrane. How
can I determine the state of electrochem equilibrium for potassium? I have
to calculate Nernst eq potential for sodium equal to -60 + 1 +log a/b giving -
60mv. So it is enough of the flow to trigger a diff in electrical potential
across the membrane
-------Now How are resting membrane potentials generated ?
- Ion channels are integral membrane proteins and in the figure these are
non gated ion channels aw leakage aw resting laino simply cz the
membrane is interrupted by these channels allowing ionic flow coupled
with water mvt
- Each ion channel represents a resistive pathway yeene it tries to impede
the flow from in to out aw out to in. a certain cannel has a certain
conductance for a specific ion called g expressed in semens. Ntebhe lal
units
- Is any ion under the influence only of Fe? Akid no. any ion flowing across
the membrane under the influence of 2 forces fd and fe. Any ion is under
the influence of a net electrochemical force
- The net driving force is the sum of Fd and Fe
- How can I use the Nernst eq to use F? the passive current triggered by the
flow of a single ion I across the ion channel is conductance x (Vm -eI )
- The membrane fiha millions of ion channels so how can I use this equation
to approximate it to physiology?
- Sodium potassium pump betfawet 2 + bettale3 3+ so fi diff in 1 + charge w
betkoun + barra
- RMP means that the membrane is under steady state conditions
- I total = I active + I passive w equal zero laino 2 vectors opp in direction
with same magnitude
- Aham shi enno at steady state the total current carried by each ion is zero
 Conduction of Ap 1:
- Dendrites or axons at resting membrane conditions have passive es
properties rm, rin, Cm.
- Capacitance exists because of electrostatic forces across the thin
membrane
- Resistance in series is due to the axoplasm significant resistane in the fiber
- Current is the passive electric property = change in charge in fuction of time
at a certain point
- Time constant: 2 electrodes are injected 1 is called current electrode to
inject the current the other records the change in membrrane potential.
- Taw is the time it takes the transmembrane pot to reach 63% of its value.
- Lambda is the distance at which the max membrane pot decays to 63 to
70% of its value. The change in voltage which is 10 mv is taking place at
point of stimulation and as the distance betwe stimulating and rec
electrode increases the voltage change decreases.
-

Generation of AP 1:
- Current is the change in charge in function of time.
- If potassium leaves the cell, its current is I+
- Exit of Cl- or entry of Na+ produce -I
- The only way a membrane voltage can be changed is by changing the
charges across that membrane
- Lambda is the distance over which max membrane potential decays to 37%
of its value or the maximal change in voltage which is 10 mv is taking place
at zero mm. as the distance between stimulation and rec electrode increase
I decreases. So lambda is a measure of how much a max voltage change dec
away from injection point.
- Taw is the time that takes AP to reach 63% of its value
- Electronic conduction: the thickness of the line is the magnitude of current.
As we move away from generator the line gets thinner yeene nb of charges
floating away from generator gets smaller meaning change in
transmembrane voltage is getting smaller and smaller.
 - Rin yeene la Na+ leaking inside and K+ leaks outside so Rm
- Myelin is a phospholipid sheet around the axon

Part 2:
- Regenerative conductance is the process by which AP are continuously
generated across the nerve fiber so AP are conducted without decrement
across nerve fiber
- They can propagate up to 1 meter or more and only effective at 5mm max.
- Our stimulus play the role of injecting electrode with current this meets the
threshold and allow the opening of Na channels
- If enough charge reaches the next patch of the membrane to depolarize it
an AP is generated so influx of Na at neighboring provides additional charge
flowing down the longitudinal axe creating a AP after reaching the
threshold.
- The delay is due to the time it takes for sodium channels to open and for it
to reach the electrode to be detected
- Ap at x1 and x2 is identical in duration and magnitude
- Nodes of ranvier are rich eza 3am nehke 3an membrane voltage channels
compared to the surface area
- L arrows yamin shmel henne flow of ions. Outward= high resistance for ions
across the myelin sheet outside
- Local currents allow the spread of depolarizations to the neighboring areas
= spread of electrotonic depolarization.
- The wave form recorded at the internode is smaller than the one recorded
at the node of Ranvier
- As the wave form is spreading towards the internode fi decrease of AP and
this is called electrotonic decrease at the internode
- Foe a myelinated nerve fiber the electrotonic decay at the internode
reduces the magnitude of the nerve form of the AP at the internode. The
electrotonic potential at the next node if 4-5 times the threshold for an AP
initiation so an AP will be generated at the next node. ]
 - So an action potential at the node of ranvier followed by an electrotonic
decay or spread of the Ap leading to a lesser magnitude at the internode
followed by the next regenartion at the node of ranvier.
- It appears as the AP at 1 ranvier jumps to the second third and 4 th node-----
saltatory action. This is much faster than regenartive conduction cz the
myelin sheath allows AP to cross the node of ranvier faster cz of the high
resistance at the internodal region and the low capacitance = myelin sheath
at the internodal area.
- As an Ap is conducted from cell body to nerve ending the local current to
not exite the proximal node to threshold cz this region entered in the
refractory phase from the prev AP
High R low conductance----saltatory mov