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Resting Membrane Potential Simulation

– Section 6 –

Case Studies

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Case Studies Background

How Membrane Depolarization and Hyperpolarization Affect Cell Sensitivity

Excitable cells must maintain a resting membrane potential (RMP) of around -70 mV to properly respond to stimuli.

Variations in ion concentrations or membrane permeability can cause the resting membrane potential to become more or less polarized, which alters the cell’s responsiveness to stimuli.

If it becomes hyperpolarized (more negative), a higher-intensity stimulus would be required to initiate an action potential (or electrochemical signal).

Animated display of resting membrane potential

Conversely, a lower-intensity stimulus would trigger an action potential if the membrane potential becomes depolarized (less negative).

Overview of Action Potentials

How Partial Repolarization After an Action Potential Affects Cell Sensitivity

To regain full sensitivity, the cell membrane must fully repolarize to its normal resting potential after an action potential. Otherwise, Na+ voltage-gated channels may not return to their resting conformation (shape) after being inactivated. If the membrane remains partially depolarized for extended periods, many Na+ voltage-gated channels may not activate (open). This condition reduces membrane excitability, often causing muscle weakness or paralysis.

Analysis Questions

1. Would an excitable cell be more or less sensitive to stimuli if its resting membrane potential becomes less polarized than normal?

2. What may happen if an excitable cell membrane does not fully repolarize while producing action potentials?

Case Studies

1. Exercise-induced Hyperkalemia

Case Subject: 

An experienced female 41-year-old marathon runner has been preparing for an upcoming race. She is healthy and trains by running several miles every other day.

Signs and Symptoms:

After a particularly long and intense training session, the subject began experiencing muscle weakness and heart arrhythmias.


After her transport to the hospital, the subject’s blood tests revealed her potassium level had risen to 7.0 mmol/l.

She was diagnosed with hyperkalemia, a condition characterized by high levels of potassium in the blood.

Hyperkalemia case study subject, Female runner

The potassium levels in an individual’s blood and extracellular fluid are usually 3.5-5.3 mmol/l, and severe manifestations typically occur when the serum potassium concentration is ≥ 7.0 mmol/l.

Due to the action of the Na+/K+ pump (ATPase), skeletal muscles contain about 80% of the intracellular potassium. Prolonged high-intensity endurance exercises can cause skeletal muscle cells to break down (rhabdomyolysis), releasing potassium into extracellular fluid.


The subject was given 5 units of insulin and 25g of glucose (to avoid low blood sugar or hypoglycemia), a standard treatment for hyperkalemia. The insulin increases the activity of the Na+/K+ pump (ATPase) proteins.

Case Study Analysis

1. Why would the subject’s extracellular K+ level increase if many of her skeletal muscle cells ruptured during exercise?

2. The subject’s potassium level rose to 7.0 mmol/l. How does this potassium concentration affect the resting membrane potential of the subject’s muscle cells? Use the GHK calculator to determine the answer.

3. Does the change in resting membrane potential make the subject’s skeletal muscle cells more or less polarized?

4. Why did the magnitude of membrane polarization change?

5. Why did the subject’s skeletal muscle cells become fatigued?

6. How did the administration of insulin help lower the extracellular potassium level?

GHK Calculator

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2. Exercise-Associated Hyponatremia (EAH)

Case Subject:

Another runner, a middle-aged male, has been training for the same marathon. He is in good health but new to endurance running.

The subject has gradually increased his exercise times to improve his endurance for the upcoming race. During his latest training session, he completed a half marathon at his top pace. It was a hot day, so he drank a large volume of regular water while running.

Signs and Symptoms: 

After his run, the subject began to feel weak, dizzy, and confused.


The subject was taken to the local hospital, where his blood results showed a sodium level of 125 mmol/l.

Hyponatremia case study subject, Male runner

He was diagnosed as having Exercise-Associated Hyponatremia (EAH), a condition that occurs when the blood sodium concentration decreases to less than 135 mmol/l.

The likely causes of the subject’s drop in blood sodium concentration were his overconsumption of hypotonic (low electrolyte) fluids, sodium lost in sweat, and an elevated level of ADH (antidiuretic hormone). In response to intense exercise, the level of ADH increases to maintain body fluids by promoting water reabsorption by the kidneys.


The subject was given 150 mL of hypertonic 3% saline to offset his low blood sodium.

Case Study Analysis

1. Did the subject’s hyponatremia change the resting membrane potential of his muscle and nerve cells? If so, by how much? Use the GHK calculator to determine the answer.

2. Would the change in resting membrane potential make the subject’s muscle and nerve cells more or less responsive to activating stimuli?

3. Would the change in resting membrane potential be a likely cause of the subject’s signs and symptoms?

4. What factor limits the impact of the subject’s hyponatremia (low blood sodium) on resting membrane potentials?

5: Because sodium also helps maintain the water balance between the extracellular and intracellular fluid compartments, would hyponatremia cause water to enter or leave cells?
(Reference: “Click here.”)

6. Could the change in water balance disrupt the functions of nerve tissues encased by the skull and cause the subject’s signs and symptoms?
(Reference: NIH – “Click here.”)

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