SESSION 3:

Ion Permeability and

Resting Membrane Potential
Main points from last session
• The body’s two compartments (ECF, ICF) are in osmotic
equilibrium, but are imbalanced chemically and
electrically.

• This imbalance is actively maintained in a steady state

and energy from this imbalance powers physiological
processes.

• Osmolarity describes number of particles per volume

solvent.
Tonicity (“stretching”)
Tonicity is a property of the solution, based on the behavior
of the cell at the initial state of the system; it answers the
question, “will the cell shrink, swell, or experience no
change in volume?”

Unlike osmolarity (OsM), tonicity has no units.

“Tonicity” is a solely a comparative term, relating the solute

content of the ECF to the ICF.
Why can’t osmolarity be used to predict
tonicity?

Osmolarity describes the concentration of all solutes

(number of particles per volume).

Tonicity depends on the concentration of NON-penetrating

solutes only.
Tonicity is assessed based on the “initial state”
of the system
non-penetrating solute
200 mOsM

400 mOsM
H 2O
Predicting tonicity
A solution is hypotonic to cell when the solution has lower
concentration of non-penetrating solutes compared to cell
A solution is hypertonic to cell when the solution has higher
concentration of non-penetrating solutes compared to cell
A solution is isotonic to cell when the cell and solution have
equal concentrations of non-penetrating solutes
Case Study
• 20-year-old otherwise healthy female college student
presented in unresponsive state with respiratory distress
after ingesting ecstasy

• Initial plasma sodium concentration was 117 mmol/L

• Diagnosis?
Hyponatremia
• Lower than normal sodium level in the
blood
• Normal sodium = 125-135 mmol/L
• Severe <125 mmol/L

• Relatively common in marathon runners

on race day

• Mild: nausea, vomiting, headache,

confusion, lethargy
• Severe: seizures, unconsciousness, coma
• Death caused by pulmonary and cerebral edema
(swelling)
Hyponatremia case treatment
• 07:00  admitted to hospital with severely low plasma [Na+]
• 10:00  20 mL 3% hypertonic saline
• 10:30  2000 mL isotonic (0.9%) saline
• 12:00  225 mL 3% hypertonic saline
• 15:30  500 mL isotonic saline
• 18:00  300 mL isotonic saline
• 20:15  Patient died 12 hours after admission

What might have been a more effective treatment plan?

The [resting] membrane potential
“Resting”: when cell is at steady state

“Potential”: electrical gradient formed between

ECF and ICF across the plasma membrane

• This stored “potential” energy, along with

chemical gradients, can be used to power
physiological processes
Forces acting on ions in solution

Chemical Force/Diffusion: ions move

from an area of high concentration to an
area of lower concentration
Forces acting on ions in solution
Electrostatic Force
• ions of opposite charge
attract
• ions of like charge repel
Membrane Channels
Ions can move across the plasma membrane via
protein channels…

Some channels are “gated” and open in response to…

• Mechanical stress
• Chemical ligands
• Voltage changes

Voltage-gated
• Usually closed
• Many are ion selective: Na+, K+, Ca2+, Cl-
• Some are charge/valence-selective: “monovalent cation channels”
Leak Channels

• Usually open
• May be ion- or charge/valence-specific
A hypothetical cell; normal physiological
situation

Na+ Na+
+
K- K+
Cl-
ACl-
A hypothetical cell

Na+ Na+
A-
K+ K+
Cl- Cl-

K+ “leaks” out of cell down its [gradient]

A hypothetical cell

Na+ Na+
A-
K+ K+
Cl- Cl-

Eventually, electrostatic attractive forces on K+

are equal and opposite to K+ chemical gradient
The Equilibrium Potential (Eion) is…

…the membrane voltage at which the

chemical and electrostatic forces on a
single ion are exactly balanced
(equal and opposite)

At this potential, a state of equilibrium is reached such

that there is no net flux of the ion across the membrane

Ions are still moving but efflux is balanced by influx

“Potential” = stored energy

Equilibrium Potential is given by the
Nernst Equation

For a given ion…

RT
E ion =
zF
ln
[ion]out
[ion]in

z = valence of the ion

Equilibrium Potential is given by the
Nernst Equation

For K+ at 37°C the equation is…

61 [ K ]out
E K 
1
log
[ K ]in

valence of the ion z = +1

Equilibrium Potential
For our artificial cell…
15 mM
E K  61 log
150 mM
 61mV

150 mM K+ 15 mM K+
If the membrane potential is more negative
than EK, there will be a net inward flux of K+

Na+ Na+
A-
K+ K+
Cl-
Cl -
Electrical force exceeds the chemical force
 K+
K+

Concentration difference across membrane determines EK

Instantaneous Em determines direction of ion flow