Resting membrane potential

Key Concepts

  • Electrochemical Gradients - Definition and Explanation

    • The concept of electrochemical gradients refers to the combined effect of the concentration gradient and the electrical gradient on the movement of ions across a membrane. This gradient is the primary driving force for ion movement across excitable cell membranes.

    • Concentration Gradient: Ions move passively from an area of high concentration to an area of low concentration, driven by random molecular motion. For example, if there is more Na^{+} outside the cell than inside, Na^{+} will tend to move into the cell.

    • Electrical Gradient: Ions move towards an area of opposite charge, or away from an area of like charge. Positive ions (cations) are attracted to negatively charged regions, and negative ions (anions) are attracted to positively charged regions. For example, if the inside of the cell is negative, positive ions like K^{+} will be electrically attracted to move into the cell.

  • Equilibrium Potential - Definition: The membrane potential at which there is no net movement of a specific ion across the membrane. At this potential, the electrical gradient perfectly opposes the concentration gradient, resulting in a state of balance where the chemical and electrical forces acting on the ion are equal and opposite.

  • Resting Membrane Potential - Definition: The electrical charge difference (voltage) across a cell's plasma membrane when the cell is at rest and not actively signaling. It is typically around -70 millivolts (mV) in human neurons and muscle cells, meaning the inside of the cell is -70 mV relative to the outside. This potential is primarily established by the differential distribution of ions and the selective permeability of the membrane to these ions, particularly potassium.

  • Membrane Permeability - Definition: The ability of a cell membrane to allow certain substances, specifically ions, to pass through it. This property is largely determined by the number and type of ion channels (e.g., leak channels, voltage-gated channels) embedded within the lipid bilayer, which selectively facilitate ion movement.

Intracellular and Extracellular Fluid

  • Electrical Disequilibrium - Definition: An imbalance of electrical charges across the cell membrane, meaning a net charge difference exists between the inside and outside of the cell. Specifically, at rest, the inside of the cell (intracellular fluid) is more negative compared to the outside (extracellular fluid).

    • Quantitative Value: Intracellular fluid is approximately -70 mV more negative compared to extracellular fluid in a typical resting neuron. This negative charge inside the cell is due to a slight excess of anions (proteins, phosphates) and a greater efflux of positive ions (K^{+}) than influx of positive ions (Na^{+}) at rest.

Ions and Their Roles

  • Cations and Anions

    • Cations: Positively charged ions, which are typically found in higher concentrations outside the cell and play crucial roles in establishing membrane potential. Examples include sodium (Na^{+}), potassium (K^{+}), and magnesium (Mg^{2+}). Mnemonic: the ‘t’ in cation resembles a plus sign.

    • Anions: Negatively charged ions, which contribute to the negative charge inside the cell. Examples include chloride (Cl^{-}) and various negatively charged proteins and phosphates within the cell. Mnemonic: the ‘n’ in anion represents ‘negative’.

Electrochemical Gradients Explained

  • Sodium and Potassium Movements - Primary Ions Involved: Sodium (Na^{+}) and Potassium (K^{+}).

    • Direction of Movement at Rest:

      • Sodium (Na^{+}): Moves from areas of high concentration outside the cell to low concentration inside the cell (down its concentration gradient). Simultaneously, the negative charge inside the cell electrically attracts the positive Na^{+} ions (down its electrical gradient). Therefore, both concentration and electrical gradients favor Na^{+} entry into the cell.

      • Potassium (K^{+}): Moves from areas of high concentration inside the cell to low concentration outside (down its concentration gradient). However, the negative charge inside the cell electrically attracts K^{+} ions back into the cell (up its electrical gradient). These two forces (concentration and electrical) act in opposing directions for potassium.

    • Both ions are influenced by:

      • Concentration Gradient: The force exerted by the difference in ion concentration across the membrane.

      • Electrical Gradient: The force exerted by the difference in electrical potential across the membrane, attracting or repelling ions based on their charge.

Example Breakdown of Potassium Movement

  1. Initial State - Imagine a membrane separating two compartments, A and B:

    • Compartment A: 4 positive ions and 4 negative ions, resulting in a net charge of 0. Also has a low concentration of K^{+}.

    • Compartment B: 4 positive ions and 4 negative ions, resulting in a net charge of 0. Contains a high concentration of K^{+}. Initially, there is no potential difference across the membrane.

  2. Insert a Potassium Leak Channel - A channel that allows only K^{+} to pass is inserted into the membrane.

    • Potassium moves from Compartment B (high K^{+} concentration) to Compartment A (low K^{+} concentration) down its concentration gradient.

    • Change in charge:

      • As K^{+} (a positive ion) leaves Compartment B and enters Compartment A, Compartment A accumulates a slight positive charge, and Compartment B becomes slightly negative.

      • Compartment A: net charge becomes +1 (e.g., 5 positive, 4 negative).

      • Compartment B: net charge becomes -1 (e.g., 3 positive, 4 negative).

  3. Consider Gradients - Now, two opposing forces act on K^{+}:

    • Concentration pull from B to A: The tendency for K^{+} to move from high concentration in B to low concentration in A persists.

    • Electrical gradient pull of K⁺ towards Compartment B: As Compartment B becomes more negative, it starts to electrically attract the positive K^{+} ions, pulling them back towards B. These forces can act in opposite directions, eventually leading to a balance (equilibrium potential).

Electrochemical Equilibrium

  • Definition: A situation for a specific ion where the net movement of ions due to the concentration gradient exactly equals and opposes the net movement due to the electrical gradient, leading to no net flow of that particular ion across the membrane.

  • Ion Equilibrium Potential: The specific membrane potential (voltage) at which these conditions hold true for a given ion. It is a theoretical potential for a single ion species.

  • Potassium Equilibrium Potential: Approximately -90 mV. This means if the membrane potential were at -90 mV, there would be no net movement of potassium ions across the membrane, as the electrical force pulling K^{+} in would exactly balance the concentration force pushing K^{+} out.

The Nernst Equation

  • Significance: Although not required for calculations in the course, understand its role: the Nernst equation is a mathematical formula that allows for the calculation of an ion's equilibrium potential, showing that the equilibrium potential is directly influenced by the ratio of intracellular versus extracellular concentrations of that ion, as well as its charge and temperature.

Combined Effect of Sodium and Potassium on Membrane Potential

  1. Equilibrium Potentials (approximate values in typical neurons):

    • Potassium (K^{+}): -90 mV

    • Sodium (Na^{+}): +60 mV

  2. Tug of War Analogy: The resting membrane potential is a weighted average of the equilibrium potentials of the ions to which the membrane is permeable.

    • Potassium (K^{+}) tends to pull the membrane potential towards its equilibrium potential of -90 mV because the resting membrane is highly permeable to K^{+} through numerous leak channels.

    • Sodium (Na^{+}) tends to pull the membrane potential towards its equilibrium potential of +60 mV, but its influence at rest is much weaker due to lower membrane permeability to Na^{+} (fewer leak channels).

    • The resulting resting membrane potential of -70 mV is closer to -90 mV (potassium's equilibrium potential) than to +60 mV (sodium's equilibrium potential), clearly indicating the significantly greater influence and permeability of the membrane to potassium ions at rest.

Membrane Permeability Summary

  • Permeability Determinants: The differential permeability of the membrane to various ions is the key factor in establishing the resting membrane potential.

    • At rest, there are significantly more open potassium leak channels than sodium leak channels present in the neuronal membrane. These channels are always open and allow ions to diffuse down their electrochemical gradients.

    • This results in a much higher permeability for potassium (approximately 40-fold greater) compared to sodium at rest, allowing K^{+} to flow out of the cell more readily than Na^{+} flows in, leading to the net negative charge inside.

Sodium-Potassium Pump (Na⁺/K⁺ ATPase)

  • Function: This active transport pump is crucial for maintaining the concentration gradients of Na^{+} and K^{+} across the cell membrane, which are essential for the resting membrane potential. With each cycle, it actively pumps 3 Na^{+} ions out of the cell and 2 K^{+} ions into the cell, against their respective electrochemical gradients, utilizing ATP as energy.

  • Importance: The pump is electrogenic because it moves $3$ positive charges out and $2$ positive charges in, leading to a net loss of one positive charge from inside the cell with each cycle. This direct contribution makes the inside of the cell slightly more negative (contributing about -3 to -5 mV to the resting potential). More importantly, by maintaining the steep concentration gradients of Na^{+} and K^{+}, the pump enables the passive diffusion of these ions through leak channels, which is the primary determinant of the -70 mV resting potential.

    • Disruptions to ion concentrations or pump function can drastically alter membrane potential, potentially impairing cell excitability.

 

  • Hyperpolarization : The membrane potential decreases (becomes more negative, moving below -70 mV). This usually occurs due to an increase in K^{+} efflux (more K^{+} leaving the cell) or Cl^{-} influx (more Cl^{-} entering the cell), making the inside of the cell even more negative.

  • Depolarization: The membrane potential increases (becomes less negative, or more positive, moving above -70 mV). This usually occurs due to an increase in Na^{+} influx (more Na^{+} entering the cell), making the inside of the cell less negative or even positive.

  • Repolarization: The process of the membrane potential returning to its resting potential (e.g., after depolarization). This typically involves the closing of Na^{+} channels and the opening or sustained activity of K^{+} channels, allowing K^{+} to leave the cell and restore the negative internal charge.

Vocabulary Recap

  • Resting Membrane Potential: The stable electrical potential across the cell membrane when the cell is not excited, typically around -70 mV.

  • Hyperpolarization: A change in membrane potential that makes the inside of the cell more negative (e.g., -80 mV), moving it further away from 0.

  • Depolarization: A change in membrane potential that makes the inside of the cell less negative or more positive (e.g., -50 mV or +30 mV), moving it closer to or past 0.

  • Repolarization: The process by which the membrane potential returns to its resting negative value following a depolarization event.