Resting Membrane Potential Simulation: Section 2
The Main Factors Affecting Resting Membrane Potentials
Introduction to the Main Affecting Factors
Two factors primarily influence the measured value of the resting membrane potential of excitable cells.
- Electrochemical gradients for potassium (K+), sodium (Na+), and chloride (Cl–).
- Concentration (chemical) gradients.
- Electrical gradients.
- Relative permeabilities of the cell membrane to these same ions.
A concentration gradient for an ion occurs when the number of that particular ion differs on either side of a cell membrane. It is commonly referred to as a chemical gradient because it is concerned with the quantity of particles, irrespective of their charge.
In excitable cells, sodium and chloride ions are more concentrated outside the cell membrane, while potassium ions and large anions, such as phosphates and proteins, are more concentrated inside the cell membrane.
The differences in concentration cause the ions to move through the cell membrane along their respective gradients from areas of higher concentration to regions of lower concentration. As these charged particles shift positions, it alters the value of the resting membrane potential.
Ion Concentration Gradients
These ion concentration gradients result from different physiological processes.
- The Na+/K+ pump actively maintains the respective concentration gradients for Na+ and K+.
- Cl– ions are passively distributed based on charge differences across the membrane resulting from the distribution of Na+ and K+.
- Large intracellular anions (phosphates and proteins) are produced inside the cell and accumulate there due to their size, which prevents them from passing through the cell membrane.
Question 1: What is an ion concentration gradient?
An ion concentration gradient occurs when the number of particles on the outside and inside of the cell membrane differ.
Question 2: What is another name for ion concentration gradients, and why is this name applied?
Ion concentration gradients are also known as chemical gradients because the gradients are based on differences in the number of particles rather than differences in charge.
Question 3: Which ions have a higher concentration outside the cell membrane?
Na+ and Cl– have higher concentrations outside the cell membrane.
Question 4: Which ions have a higher concentration inside the cell membrane?
K+ and large anions (phosphates and proteins) have higher concentrations outside the cell membrane.
Question 5: How do the ion concentration gradients affect the resting membrane potential?
The ions move through the cell membrane along their respective gradients from areas of higher concentration to regions of lower concentration. As the charged particles shift positions, the value of the resting membrane potential changes.
Question 6: What maintains the gradients for Na+ and K+?
The sodium-potassium pump (Na+/K+ ATPase) actively maintains the gradients for Na+ and K+ ions.
Question 7: How is the gradient for Cl– ions established?
Cl– ions are passively distributed based on charge differences across the membrane resulting from the distribution of Na+ and K+.
Question 8: Why do large anions like phosphates and proteins accumulate inside the membrane?
They are produced inside the cell and are too large to pass through the membrane.
An electrical gradient develops when there is a difference in the electrical charge between the interior and exterior of a cell membrane. This imbalance develops when ions move across the cell membrane along their concentration gradient, causing particles with the same charge to accumulate on the opposite side of the membrane.
The increase in charge on the opposite side of the membrane repels similarly charged ions from entering. As ions continue to move across the cell membrane, the repelling force of the electrical gradient increases. When the opposing gradients reach an equilibrium, ions move back and forth across the cell membrane in equal proportions.
Concentration and Electrical Gradients at Equilibrium
Question 1: What is an electrical gradient?
An electrical gradient develops when there is a difference in the electrical charge between the interior and exterior of a cell membrane.
Question 2: How is an electrical gradient produced?
An electrical gradient develops when ions move across the cell membrane along their concentration gradient, causing particles with the same charge to accumulate on the opposite side of the membrane.
Question 3: How does the electrical gradient affect the movement of ions down their concentration gradient?
The increase in charge on the opposite side of the membrane repels similarly charged ions from entering.
More About Concentration Gradient and Electrical Gradient Interactions
Let us investigate the interaction between concentration and electrical gradients using K+ ions. We will focus on K+ because the cell membranes of excitable cells are highly permeable to this ion, which significantly affects the resting membrane potential.
The following diagram shows a cell membrane consisting of a lipid bilayer without channels or other embedded proteins. A higher concentration of K+ ions exits inside the membrane than outside. This distribution produces an outward K+ concentration gradient.
Adding negatively charged particles (anions) eliminates the charge on either side of the membrane. Each is neutral because the number of anions equals the number of cations. Therefore, there is no electrical gradient, and the membrane potential is 0 mV.
Use this activity to create content.
Question 1: What conditions make both sides of the membrane neutral?
Both sides of the membrane become neutral by adding enough anions to equal the number of K+ ions (cations).
Question 2: Why is there no electrical gradient?
An electrical gradient is absent because there is no difference in charge between the inside and outside of the cell membrane.
Question 3: Why is the membrane equilibrium potential 0 mV?
The membrane potential is 0 mv because there is no electrical gradient.
Adding potassium leak channels to the membrane provides a pathway for K+ ions to exit the cell along their concentration gradient while the anions remain in place. The outward flow of K+ ions makes the cell’s external environment positively charged and the internal environment negatively charged, creating an inward electrical gradient.
As K+ ions continue their outward flow, the charges on either side of the membrane increase. As a result, the growing inward electrical gradient creates an opposing force that makes it increasingly difficult for potassium ions (K+) to move across the cell membrane. The outer positive charge increasingly repels the K+ ions, while the inner negative charge increasingly attracts them.
Use this activity to create content.
Question 1: What pathway allows the K+ ions to cross the membrane?
The K+ ions cross the membrane through open leak channels.
Question 2: What causes the K+ ions to move outside the cell membrane?
The K+ ions move outward down their concentration gradient.
Question 3: Does a concentration gradient exist for the anions? If so, what direction is the gradient?
Yes, the anions have an outward concentration gradient.
Question 4: What prevents the anions from crossing the membrane?
The membrane does not contain any channels for the ions.
Question 5: What causes an electrical gradient to develop for the K+ ions?
The outward flow of K+ ions makes the cell’s external environment positively charged and the internal environment negatively charged.
Question 6: In what direction is the electrical gradient for K+?
The direction of the electrical gradient is inward.
Question 7: What causes the magnitude of the electrical potential to grow?
The magnitude of the electrical gradient grows as K+ ions continue to exit the cell, adding to the exterior’s positive charge and the interior’s negative charge.
An ion, like K+, attains an equilibrium state when the force of its electrical gradient equals the force of its opposing concentration gradient.
The electrical potential at this stage is the ion’s equilibrium potential, and its magnitude is directly proportional to the initial ion concentration. The larger the initial concentration gradient, the greater the equilibrium potential to offset the flow of ions through the membrane.
Although ions continue to move across the membrane at equilibrium, the exchange remains balanced, with no net gain on either side.
Use this activity to create content.
Question 1: At what point is an equilibrium achieved between an ion’s concentration and electrical gradients?
An equilibrium is achieved when the force of an ion’s electrical gradient equals the opposing force of an ion’s concentration gradient.
Question 2: What is an ion’s equilibrium potential?
An ion’s equilibrium potential is the electrical potential that exactly offsets an ion’s opposing concentration gradient.
Question 3: Do ions stop moving across the membrane once equilibrium is attained?
No, ions continue to move across the membrane at equilibrium. However, the exchange is balanced, with no net gain on either side of the membrane.
Ion Membrane Permeability
The concentration gradient is the force that drives ions across the cell membrane. However, the quantity of open ion channels in the membrane determines its permeability.
The permeability of a cell membrane to ions is comparable to how floodgates control water flow through a dam. In a dam, the water level represents the ion’s concentration gradient, with a higher concentration on one side and a lower concentration on the other. The dam’s floodgates are analogous to the ion channels in the cell membrane. When the floodgates are closed, water cannot flow through, just as ions cannot pass through a cell membrane when ion channels are absent. When the floodgates open, water flows from the side of higher concentration to the side of lower concentration, similar to ions moving down their concentration gradient through open leak channels. The amount of water that can flow through the dam is determined by the number of open floodgates, just as the number of open ion channels influences the rate of ion movement across the cell membrane.
Below is a list of ions and their relative membrane permeability values. Because excitable cell membranes are most permeable to K+, this ion’s permeability value is 1. The Na+ and Cl– values indicate how permeable these ions are relative to K+ (PK).
0.3 – 0.5
0.05 – 0.01
Question 1: How much less permeable is the membrane to Na+ ions than to K+ ions? Determine your answer using PK / PNa.
The membrane is about 20 to 100 times less permeable to Na+ than to K+.
Question 2: How much less permeable is the membrane to Cl– ions than to K+ ions? Determine your answer using PK / PCl.
The membrane is about 2 to 3 times less permeable to Cl– than to K+.
Human Bio Media materials are open-source and can be adapted and shared by anyone according to the Creative Commons Attribution 4.0 License guidelines.
If you are redistributing Human Bio Media materials in print or digital formats, you should include on every page the following attribution:
Access this content for free at https://humanbiomedia.org
References and Attributions
Click here to view the reference list.
1. Advances in Physiology Education – “Generation of resting membrane potential.”
2. Clinical Journal of the American Society of Nephrology – “A Critically Swift Response: Insulin-Stimulated Potassium and Glucose Transport in Skeletal Muscle.”
3. European Society of Cardiology – “Hyperkalemia, the sodium-potassium pump and the heart.”
4. Gatorade Sports Science Institute – Hyponatremia in Athletes.”
5. Hindawi Case Reports in Medicine – “Acute Ascending Muscle Weakness Secondary to Medication-Induced Hyperkalemia.”
6. Lab Exchange – “Membrane bilayers are permeable to small, uncharged molecules.”
7. Lippincott Learning – “Concentration and Volume: Understanding Sodium and Water in the Body.”
8. Journal of the Association of Physicians in India – “Severe Muscle Weakness due to Hyperkalemia.”
9. McGill Medicine and Health Sciences – “Resting Membrane Potential.”
10. Medical Neuroscience – “Action Potential.”
11. Michigan State University Library – “Foundations of Neuroscience.”
12. N. I. H. National Library of Medicine – “The Electrophysiology of Hypo- and Hyperkalemia.”
13. N. I. H. National Library of Medicine – “Extracellular Potassium Homeostasis: Insights from Hypokalemic Periodic Paralysis.”
14. N. I. H. National Library of Medicine – “Getting Across the Cell Membrane: An Overview for Small Molecules, Peptides, and Proteins.”
15. N. I. H. National Library of Medicine – “Hyperkalemia.”
16. N. I. H. National Library of Medicine – “Hyponatremia and the Brain.”
17. N. I. H. National Library of Medicine – “Ion Channels and the Electrical Properties of Membranes.”
18. N. I. H. National Library of Medicine – “Physiology, Resting Potential.”
19. N. I. H. National Library of Medicine – “Physiology, Sodium Potassium Pump.”
20. N. I. H. National Library of Medicine – “Principles of Membrane Transport.”
21. N. I. H. National Library of Medicine – “Structure of the Plasma Membrane.”
22. N. I. H. National Library of Medicine – “Transport of Small Molecules.”
23. Nursing 2020 Critical Care – “Electrolytes Series: Potassium.”
24. Nursing 2020 Critical Care – “Electrolytes Series: Sodium and Chloride.”
26. Saudi Journal of Kidney Diseases and Transplantation – “Hyperkalemia Revisited.”
28. ScienceDirect – “Membrane Potential.”
29. ScienceDirect – “Skeletal Muscle Physiology.”
30. University of New Mexico – “Ionic gradients, membrane potential and ionic currents.”
31. University of St. Andrews – “Neurosims.”
32. University of St. Andrews – “The Origin of the Resting Membrane Potential.”