1. The Membrane Potential
Results from:
(1) action of Na-K pump
(2) permeability of PM (leakage channels)
(3) presence of impermeant molecules (fixed anions)
yields an observed “charge” at the PM (outside is slightly more positive, inside is slightly more negative)
leakage channels + -
membrane potential
Potential: 2 oppositely charged molecules separated by something. Impt because it is potential energy (stored energy)
Orange = sodium purple = potassium. Stars = fixed anions (stable negatively charged; many proteins in cells)
Establish membrane potential Na-K pump creates a concentration gradient (pump Na out; K in) (sodium wants to flow inside; potassium is high inside, so wants to flow outside)
Use leakage channels: unequal distribution of charges across PM, because there is a tendancy for K to leak more easily than Na. add up charge, is equal. Open channels of the PM
Leak allows K to flow out. (K has a positive charge). Occurs at the plasma membrane
Fixed anions: draws cations into cell
fixed anions Na K

2. The Membrane Potential of a Cell
For a cell:
Na-K pump
leakage channels
fixed anions
Around PM, where leakage is occuring, we get + on outside – on inside. Why? Because K (a positive charge) is leaving the cell. Plasma membrane is more permeable to K
difference in charge, or potential difference, is the membrane potential; denoted in volts
primarily determined by K conc gradient
*is only observed at the PM*

3. Equilibrium Potentials
many inorganic ions maintained at specific conc’s within IC & EC
contributes to membrane potential, impact of each ion depends on it’s:
conc gradient
membrane permeability K
major role in membrane potential
PM more permeable to this ion
consider membrane only permeable to K, what would be the membrane potential?
K equilibrium potential, EK
-90mV (with an internal concen of 150 and external of 5) As the membrane potential is -90, K will not move.
Na equilibrium potential, ENa
66 mV (when concentration is 145 outside and 12 mM inside) Na will not move
equilibrium
Conc gradient and permeability impact how things move across pm
Cells control this and use it for communication purpose (impt in excitable cells aka neurons and muscle cells)
Answer:
Fixed anions want to draw K back in
Where K conc is stable, ie no net flow of ion (its at equilibrium). Find membrane potential [K] stable. Trying to find equilibrium potential

4. example – an excitable cell
equilibrium potentials are useful for they explain what happens when the PM becomes more permeable to a particular ion
example – an excitable cell
permeable to Na, brief pd; membrane potential moves toward ENa
at rest
-70mV
Neuron, apply voltage, and causes a change in permeability to Na. Move toward Ena
YET, the membrane potential at rest is close but not the same as the EK

5. Nernst Equation EX = _______ log ______
diffusion gradients of an ion depend on conc differences
equilibrium potential depends on ratio of ion conc on both sides of PM
Nernst equation
permits calculation of theoretical equilibrium potential for specific ion
conc’s known
differ between ion species
magnitude & direction
cation
value negative
Xi > Xo (internal conc greater than outside)
K is (-90) high inside cell
Na is (66) high outside cell
yet, what happens when more than one ion channel is open?
GHK equation (Vm) 61
[Xo]
EX = _______ log ______ z
[Xi]
61 mM
= ____ log __5___ = mM
= _61_log _____ = mV +1
Allows us to calculate the electrical potential necessary to balance a given ion conc gradient across PM so no net flux of the ion occurs. Adjust permeability of the PM
Z = valance of ion.

6. Goldman-Hodgkin-Katz equation (Vm)
Reversed due to Cl is an anion mvt has oppositite effect on membrane
PK [Ko] + PNa[Nao] + PCl[Cli]
Vm = 61 log
PK [Ki] + PNa[Nai] + PCl[Clo]
(1)(5) + (0.04)(145) + (0.45)(9)
= 61 log = -68 mV
(1)(150) + (0.04)(12) + (0.45)(125)
Pk Potassium permeability constant
Na is least permeable, K is most permeable, Cl is in the middle
Cl is an anion (negatively charged), so has different impact on PM
Reversed due to Cl is an anion mvt has oppositite effect on membrane
K highest permeability, explains wny RMP close to Ek

7. Resting Membrane Potential (RMP)
membrane potential of a cell at “rest”, or a cell in an inactivated state
depends on:
ratio of conc’s (Xo/Xi) of each ion on both sides of PM
specific permeability of membrane to each ion
most impt “players”
K+, Na+, Ca2+ & Cl-
individual contribution dependent on conc differences across PM (can change depending on cell type, tissue or organ) & permeabilities
any change in an ions EC conc will change the RMP but only to the extent the membrane is permeable (you can mess with Na conc gradient, but have more impact if you mess with K)
change in the cell membranes permeability for any given ion will change its RMP
excitable cells
cellular range
-65 mV to -85 mV

8. Question
Would lowering a neuron’s IC [K] by 1 mM have the same effect on RMP as raising the EC [K] by 1 mM?
Confirm with Nernst equation
-No; Changing the EC [K] has a greater effect on Ek and thus the RMP. This is because of the ratio of external to internal K is changed more when EC levels go from 5 to 6 mM (20% increase) than IC level lowered from 150 to 149 mM (0.7% increase)
No because if

9. leakage channels always open
Role of Na-K pumps
RMP is less than the EK suggest that K leaks out & cell not at equilibrium with respect to K conc, or Na conc either
ion leakage + EE, results in membrane potential
leakage channels always open
runs continuously
What might be impacting RMP? Not just K leakage, also the electrogenic effect.
Na-K pump: you are not moving the same number of positive charge. Electrogenic pump, because it causes an electrogenic effect: unequal transport of charge).
Makes outside more positive.
RMP is never at K equlibrium potential
Na-K pump creates electrogenic effect because it does not pump equal amounts of + and – charge. Helps establish positive on outside; negative on inside
If outside is positive and inside is negative. Positive charge will want to flow across (inside) and negative will want to flow outside
maintains ion conc’s
electrogenic effect
unequal transport of + charge (3Na to 2K) by Na-K pump, makes inside “less” positive, or negative
MINIMAL on RMP
counters leakage

10. Influences on RMP Fixed negative charge (wants to draw + charge to it)
Because of pump make K higher inside Na higher outside
Permeability, leakage of K has the MOST effect, electro pump has an effect as well.

11. Cell Signaling refers to how cells communicate with each other
intercellular communication
many release regulatory molecules into EC environment
general categories
paracrine
synaptic
endocrine
Paracrine regulator: regulator molecule released from one cell and effects another cell
Synaptic: Directly send messenger from one cell to another
Endocrine: Release regulatory molecule to EF, transport through blood or lymphatics, to wherever its target tissue (organ is located)
local mechanism
functional connection
long distance

12. A = autocrine
Autocrine: cell releases reg. molecule that then feeds back on itself.
Gap junctions: directly comm. From one cell to another. Flow for fusion of Intracellular space from one cell to another. Can be opened or closed (regulated)
GAP JUNCTIONS provide direct communication between cells by fusing PMs and permitting diffusion from one cell’s cytoplasm to the next

13. target cell must display a R protein for signaling/regulatory molecule
Regulatory Molecules
LOCATION
Target cell: effected by regulatory molecule if it has a signal.
More of a change in the extracellular than intracellular to get to the normal Ek
Target cell if it has a receptor like cell A. Must have receptor for signaling molecules
Neurotransmitters, hormones, paracringe regulators: must decide if they are polar (water soluble) or nonpolar (lipid soluble)
Nonpolar (lipid soluble) go right through. Found in the cytoplasm or nucleus.
target cell
target cell must display a R protein for signaling/regulatory molecule

14. Signal Transduction Pathways
mech for water soluble msgers
2nd messenger systems
Regulatory molecules is first messenger, bind to receptor and initiate a second messenger
Panel d: g protein. Hormone binds to receptor, activates g protein, alpha subunit then activates effector protein, second messenger then has cellular response
Regulatory molecule binds to receptor  activated state  effectors (alpha or beta)  unstimulated state
A) open ion channel b) becomes activated enzyme c)binds to receptor, activate enzyme bound to it

15. Signal Transduction Pathways
mech for lipid-soluble msger
transcription factor
Go across pm, bind to receptor intracellularly. A lot of times found in the nucleus and serves as a transcription factor. Message then goes out; transcribe, translate and end up with synthesis of a protein that is then going to cause cellular response

16. Cessation of Activity in Signal Transduction
impt b/c chronic overstimulation can be detrimental to cell
detrimental to the cell
key event is stopping R activation
(1) decrease conc of 1st msger
(2) R becomes chemically altered, lowers affinity for 1st msger
(3) R becomes phosphorylated, prevents G-protein binding
(4) R-ligand complex endocytosed, removed R from PM
Happens for as long as reg molecule is bound to the receptor
Decrease conc of 1st messenger (quit making reg molecule and you will have stopping of simple transduction pathway
2) seen in water soluble category
4) if we don’t have receptor on pm, target cell will not respond to reg. molecule.
Mechanisms utilized to stop signal transduction pathways.