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)

-+

membrane potential

leakage channels

Na Kfixed anions

2

difference in charge, or potential difference, is the

membrane potential; denoted in volts

primarily determined by K conc gradient

For a cell:

Na-K pump

leakage channels

fixed anions

The Membrane Potentialof a Cell

*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

4

equilibrium potentials are useful for they explain what happens when the PM becomes more permeable to a particular ion

example – an excitable cell

at rest

-70mV

permeable to Na, brief pd; membrane potential

moves toward ENa

YET, the membrane potential at rest is close

but not the same as the EK

5

Nernst Equation

• 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)

EX = _______ log ______61

z

[Xo]

[Xi]

61 mM= ____ log __5___ = -90 +1 150 mM

= _61_log _____ = +66 mV +1

6

– Goldman-Hodgkin-Katz equation (Vm)

Vm = 61 logPK [Ko] + PNa[Nao] + PCl[Cli]

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)

Reversed due to Cl is an anion mvt has oppositite effect on membrane

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

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

8

-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)

9

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

runs continuously

maintains ion conc’s

counters leakage

electrogenic effect

unequal transport of + charge (3Na to 2K) by Na-K pump, makes inside “less” positive, or negative

MINIMAL on RMP

leakage channels always open

ion leakage + EE, results in

membrane potential

10

Influences on RMP

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

local mechanism

functional connection

long distance

12

A = autocrine

GAP JUNCTIONS provide direct communication between cells by

fusing PMs and permitting diffusion from one cell’s cytoplasm to the next

13

Regulatory Molecules

target cell

target cell must display a R protein for signaling/regulatory molecule

LOCATION

14

Signal Transduction Pathways

mech for water soluble msgers

2nd messenger systems

15

Signal Transduction Pathways

transcription factor

mech for lipid-soluble msger

Cessation of Activity in Signal Transduction

16

• 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