Resting Membrane Potential - Comprehensive Notes
The Brain's Environment: Water, Ions, and Membranes
Water is the brain’s major solvent (about 75% of brain mass).
Water is a polar molecule: Oxygen pulls more electron density than hydrogen, giving oxygen a partial negative charge and hydrogens a partial positive charge.
Polar water molecules form hydration shells around ions, stabilizing them in solution.
If water weren't polar, solvation and ion transport in the brain would be drastically different, impacting signaling and homeostasis.
Water, Polarity, and Its Role in Neural Function
The polarity of water underlies its solvent properties and enables hydration of ions.
Hydration shells (clouds of water around ions) reduce ion–ion interactions and influence ion mobility.
Ions love water because the water molecules stabilize their charge through hydration.
Ions and Hydration
Ions are atoms or molecules with a net electric charge.
Cations: net positive charge (examples: Na⁺, K⁺, Ca²⁺).
Anions: net negative charge (example: Cl⁻).
In water, ions dissociate and are surrounded by hydration shells; the individual ions are more attracted to water than to each other, forming a hydration sphere.
The Phospholipid Membrane
The membrane is a bilayer of phospholipids with a hydrophilic phosphate head (polar) facing water and a hydrophobic lipid tail (nonpolar) forming the interior.
Hydrophobic compounds and small uncharged polar molecules can pass through more easily than charged species.
Ion passage requires specific pathways in the membrane—typically transmembrane proteins.
Proteins and Amino Acids: Building Blocks for Membrane Transport
Proteins are built from amino acids and serve as enzymes, cytoskeleton components, receptors, channels, pumps, etc.
Amino acid properties determine mature structure, protein–protein interactions, and interactions with membranes.
R-groups (side chains) are unique and drive folding, localization, and function.
Why Would a Protein Be in a Membrane?
Amino acids that associate with lipids vs. water vs. charged molecules influence whether a protein embeds in the membrane or resides in the aqueous interior/exterior.
Is the Amino Acid Sequence THAT Important?
Ava’s case (context used in the lecture):
Her Na⁺/K⁺ pumps are mislocalized to the membrane (ICC showed mislocalization).
Her resting membrane potential (RMP) was abnormally high compared to healthy cells.
A possible link to the pump’s amino acid sequence being wrong, affecting trafficking and function.
The Na⁺/K⁺ Pump: Structure and Function
The Na⁺/K⁺ pump is an ion pump that uses ATP to move ions against their gradients:
3 Na⁺ ions out of the cell per ATP hydrolyzed
2 K⁺ ions into the cell per ATP hydrolyzed
The pump is a membrane-spanning protein complex composed of subunits (e.g., ATP1A1 as the alpha subunit; FXYD regulatory subunits exist).
The pump’s proper localization to the membrane is crucial for maintaining the resting membrane potential and ion homeostasis.
In Ava’s case, mislocalization of the pump would disrupt Na⁺/K⁺ balance and RMP.
Ion Channels vs Ion Pumps
Two main membrane-spanning protein types:
Ion pumps: consume ATP to move ions against their concentration gradients (e.g., Na⁺/K⁺ ATPase, Ca²⁺ pump).
Ion channels: allow ions to diffuse down their electrochemical gradients.
Channel types:
Voltage-dependent channels open/close in response to membrane potential changes.
Ligand-gated channels open/close in response to chemical binding.
Characteristics of ion pumps vs channels:
Pumps require ATP; channels do not.
Pumps move ions against gradients; channels permit passive diffusion down gradients.
Channels can be gated; pumps are typically always active (though regulated by cellular signals).
The Resting Membrane Potential: Conceptual Basis
Resting membrane potential (RMP) arises from the combined influence of water hydration, membrane permeability, and the distribution of ions across the membrane.
Water’s polarity and the inability of ions to move freely through the hydrophobic membrane interior necessitate membrane pathways for ion movement.
Specific membrane proteins create selective pathways that determine which ions move more readily.
The asymmetry in ion permeabilities and concentrations creates a charge separation across the membrane, establishing an RMP around -70 mV (value varies by neuron).
Nernst Equation: Ion-Specific Equilibrium Potentials
The Nernst equation gives the equilibrium potential for a single ion when the membrane is permeable only to that ion.
General form (at 37°C):
E{ ext{ion}} = z imes rac{RT}{F} imes ext{ln}iggl( rac{[ ext{ion}]{ ext{out}}}{[ ext{ion}]_{ ext{in}}}iggr)At 37°C, this is commonly simplified to:
E{ ext{ion}} = 61.54 imes ext{log}{10}iggl( rac{[ ext{ion}]{ ext{out}}}{[ ext{ion}]{ ext{in}}}iggr)Example: Potassium (K⁺) with typical concentrations shows a resting potential around -80 mV when the membrane were only permeable to K⁺.
For K⁺: EK = 61.54 imes ext{log}{10}iggl( rac{[ ext{K}^+]{ ext{out}}}{[ ext{K}^+]{ ext{in}}}iggr)
If [K⁺]out = 4 mM and [K⁺]in = 140 mM, then approximately:
E_K
oughly
ightarrow -95 ext{ mV}If [K⁺]out = 40 mM and [K⁺]in = 140 mM, then approximately:
E_K
oughly
ightarrow -33 ext{ mV}
Driving Forces and Current: When Do I Move?
A current is generated only if three conditions are met:
There must be ions to carry charge (ions present).
There must be a passageway (an open/available ion channel).
There must be a driving force (concentration gradient and/or voltage).
The relation between current, conductance, and driving force:
I{ ext{ion}} = g{ ext{ion}} (Vm - E{ ext{ion}})In other words, Current = conductance × driving force. If there is no conductance or no driving force, there is no current.
Multiple Ions at Rest: Why Not Just EK or ENa?
At rest, multiple ions can move, but not all at their equilibrium potentials because:
The membrane is not exclusively permeable to one ion; it has finite permeabilities for several ions.
Channels are not always open; there's a baseline permeability for several ions.
The resting potential results from the weighted contribution of multiple ions with their respective permeabilities, not simply the sum of independent Nernst potentials.
Goldman-Hodgkin-Katz (GHK) Equation: A Multion View
When more than one ion can move at rest, the Goldman equation provides a more comprehensive prediction of Vm by accounting for charge, concentrations, and relative permeabilities:
Vm = 61.54 imes ext{log}{10}iggl( rac{PK [K^+]{ ext{out}} + P{Na} [Na^+]{ ext{out}}}{PK [K^+]{ ext{in}} + P{Na} [Na^+]{ ext{in}}} iggr)The membrane potential is pulled toward each ion’s equilibrium by its permeability:
Potassium permeability (PK) pulls Vm toward EK.
Sodium permeability (PNa) pulls Vm toward ENa.
Changes in permeability (e.g., channel opening/closing) alter Vm.
The full GHK form can include other ions (e.g., Cl⁻) with their permeabilities; the two-ion form is a common simplified version.
How the Goldman Equation Helps Predict the Resting Potential
If extracellular potassium concentration [K⁺]out is varied, Vm tends to depolarize (move toward 0 mV) as [K⁺]out increases.
The Nernst prediction for Vm when only K⁺ is permeable does not perfectly match actual Vm at rest because other ions (Na⁺, Cl⁻) still carry current.
In practice, Vm at rest lies somewhere between the individual ion equilibrium potentials, weighted by their relative permeabilities.
What Ion Sets the Resting Membrane Potential? A Practical View
If Na⁺ equilibrium is +62 mV and the resting Vm is around -68 to -70 mV, current arises from a combination of conductances for Na⁺ and K⁺.
The ion with the greatest driving force and highest conductance at rest contributes most to the resting current, but it is a balance of all permeant ions.
Example questions asked in the lectures:
With Vm at -68 mV and E_K ≈ -80 mV, which ion dominates the resting current given their conductances?
How does changing extracellular K⁺ alter the driving force for K⁺ and hence Vm?
Potassium Homeostasis in the Brain: Regulation of Extracellular [K⁺]
Mechanisms regulating external K⁺ concentration include:
The blood–brain barrier restricting ion movement between blood and brain tissue.
Potassium spatial buffering by astrocytes: astrocytes take up excess K⁺ and distribute it through their networks.
Astrocytes possess pumps to concentrate K⁺ intracellularly and can dissipate it through their extensive processes.
This buffering helps prevent excessive depolarization and maintains stable neuronal excitability.
Real-World Context: Learning, Ethics, and Applications
The lecture includes a slide on lethal injection to illustrate the physiological consequences of membrane potential disruption and rapid ion flow on vital functions (blood circulation, breathing, heart activity).
Understanding ion gradients and membrane potentials is foundational for pharmacology, neurology, and medical ethics discussions about interventions that alter neural activity.
Think, Pair, Share: Quick Review Questions
At rest, where are Na⁺ and K⁺ predominantly located relative to the cell?
What causes ions to move at rest?
Which ion moves the most at rest, and what is the resting membrane potential approximately?
How is the resting membrane potential maintained?
Nernst Equation: Quick Practice Revisit
For K⁺ (example):
If outside = 4 and inside = 140, then
EK = 61.54 imes ext{log}{10}iggl( rac{4}{140}iggr)
ightarrow ext{approximately } -95 ext{ mV}
If outside = 40 and inside = 140, then
EK = 61.54 imes ext{log}{10}iggl( rac{40}{140}iggr)
ightarrow ext{approximately } -33 ext{ mV}
Chapter 3 Learning Objectives ( summarized )
Describe ion channels versus pumps, and why some require ATP.
Explain the role of amino acids in protein structure and membrane interactions.
Describe electrochemical forces and membrane potential V(m).
Define diffusion vs. electrostatic (driving) forces.
Define equilibrium potential and driving force.
Explain when a membrane reaches an ion's equilibrium potential.
Understand current flow at EK (as an example).
Describe outcomes if an ion is not at its equilibrium potential and the factors that influence this.
Distinguish between Nernst and GHK potentials.
Explain how resting membrane potential is maintained and why it is around -70 mV (varying by neuron type).
Analyze how changing K⁺ or Na⁺ concentrations affects resting membrane potential and action potential.