Resting Membrane Potential Simulation
– Section 6 –
Case Studies
Links to Other Sections
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).
Conversely, a lower-intensity stimulus would trigger an action potential if the membrane potential becomes depolarized (less negative).
Overview of Action Potentials
An action potential is a momentary and sudden spike or reversal in the membrane potential that serves as an electrochemical signal.
1. This process begins when a stimulus causes the cell membrane to depolarize to a threshold level, typically around -55 mV.
2. The change in membrane potential activates (opens) sodium (Na+) voltage-gated channels embedded in the membrane.
3. As a result, Na+ ions flow into the cell through the channels, and the membrane potential rapidly depolarizes.
4. When the membrane potential reaches approximately +30 mV, the Na+ channels self-inactivate (close), while potassium (K+) channels open.
5. The rapid outward flow of K+ ions through the channels repolarizes the membrane.
Channel States During An Action Potential
6. When the membrane returns to its normal resting potential, Na+ channels revert to their original resting state, allowing the activation process to begin again.
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?
The membrane would become more sensitive.
2. What may happen if an excitable cell membrane does not fully repolarize while producing action potentials?
After being inactivated, the Na+ channels may not return to their resting conformation (shape), causing them to remain inactive.
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.
Diagnosis:
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.
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.
Treatment:
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?
The skeletal muscles contain about 80% of the intracellular potassium. The potassium would be released into the extracellular fluids if these cells rupture.
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.
The resting membrane potential of the subject’s muscle and nerve cells would decrease to about -65 mV (from -70 mV).
3. Does the change in resting membrane potential make the subject’s skeletal muscle cells more or less polarized?
The subject’s skeletal muscle cells became less polarized (partially depolarized).
4. Why did the magnitude of membrane polarization change?
The magnitude of membrane polarization changed because the increase in extracellular K+ made the outer environment of the muscle cells more positive, reducing the difference in charge across the membrane.
5. Why did the subject’s skeletal muscle cells become fatigued?
The cell membranes of the subject’s skeletal muscle cells remained partially depolarized for a prolonged period. This condition prevented the reactivation of many membrane-embedded Na+ voltage-gated channels, making it more difficult to initiate action potentials.
6. How did the administration of insulin help lower the extracellular potassium level?
The insulin increased the activity of the Na+/K+ pump (ATPase) proteins. As a result, the pump proteins transported K+ ions into the subject’s cells from the extracellular environment.
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.
Diagnosis:
The subject was taken to the local hospital, where his blood results showed a sodium level of 125 mmol/l.
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.
Treatment:
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.
The resting membrane potential of the subject’s muscle and nerve cells increased to about -71 mV (from -70 mV).
2. Would the change in resting membrane potential make the subject’s muscle and nerve cells more or less responsive to activating stimuli?
The cell membranes become slightly more polarized (hyperpolarized), making the cells less responsive.
3. Would the change in resting membrane potential be a likely cause of the subject’s signs and symptoms?
The slight change in the resting membrane potential is insignificant and not the 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?
The membranes of excitable cells have relatively few Na+ leak (open) channels, reducing their permeability to this ion.
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.”)
Hyponatremia (low Na+ concentration) makes the extracellular fluids hypotonic, causing water to enter cells by osmosis.
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.”)
Yes. Water entering brain tissues causes them to swell inside the skull. The resulting pressure causes tissue damage and functional impairment.
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References
Click here to view the reference list.
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