Ion Channels and Resting Membrane Potential

Lecture Objectives

• List the six major types of transmembrane proteins.
• Describe the different types of ion channels present in the nervous system (leak, ligand-gated, mechanically gated, and voltage-gated).
• State the typical intracellular and extracellular concentrations of potassium, sodium, chloride, and calcium.
• List the different types of gated ion channels and describe how the density of different types of gated ion channels typically vary from one part of a neuron to another.
• Explain how resting membrane potential is established in neuronal cells.
• Understand how equilibrium potential is related to both chemical concentration and electrical gradients.
• Describe how changes in membrane ion permeability alter the membrane potential.
• Recognize that membrane potential will be closest to the equilibrium potential of the ionic species that it is most permeable to.

Outline

• Part 1:
  • Ion Channels and Transporters contributing to transmembrane potential
  • Electrochemical Equilibrium
• Part 2:
  • Calculating equilibrium potential
  • Determining resting membrane potential

Membrane Proteins

• Major determinants of cell function.
• Six types of transmembrane proteins:
  1. Anchoring proteins
  2. Recognition proteins
  3. Enzymes
  4. Receptor proteins
  5. Carrier proteins
  6. Channel proteins (a.k.a. ion channels)
• Critical determinant of transmembrane ion movements (and thus ion concentrations).

Resting Membrane Potential (RMP)

• A resting membrane potential (RMP) can be recorded from all living cells.

Transmembrane Potential (Vm)

• Resting conditions: cells have a potential difference across their plasma membrane = Resting Membrane Potential (RMP).
• By convention, voltage of extracellular fluid = 0, and the polarity (+ or -) of membrane potential stated in terms of charge on the inside of the plasma membrane (e.g., -70mV).

Factors Contributing to RMP in Neurons

1. $Na^+/K^+$ pumps
2. Unequal distribution of ions across the plasma membrane & selective membrane permeability to $Na^+$ and $K^+$
3. Most anions cannot leave the cell

Typical Ion Concentrations (mM)

• Intracellular fluid (ICF) and extracellular fluid (ECF) (NB: precise values vary from text to text)
  • $K^+$: ICF = 150, ECF = 5
  • $Na^+$: ICF = 15, ECF = 150
  • $Ca^{++}$: ICF = <10-6 (M), ECF = 2
  • $Cl^-$: ICF = 5, ECF = 110
• Concentration gradients of some ions are maintained by carrier proteins (e.g., the $Na^+/K^+$ pump).

Establishing Concentration Gradients

• The ATP-driven, $Na^+/K^+$ exchange pump establishes $Na^+$ & $K^+$ concentration gradients that are critical to the establishment of membrane potential.
• Note that $Na^+$ & $K^+$ are both being moved “uphill”.

Leaky Ion Channels

• Channel randomly opens and closes (Ungated).

Electrochemical Equilibrium for $K^+$

• What happens if $K^+$ on one side of the cell membrane is permeable to $K^+$ but not $A^-$ (proteins, phosphate, etc.)?
  • $K^+$ will diffuse DOWN its chemical gradient, taking positive charge with it.
  • This generates an electrical gradient that is detected by the voltmeter.
  • (The inside of the cell has more -ve charges than the outside of the cell, -90mV)
  • $A^-$ will not move due to limited permeability.
• Q: How much $K^+$ will move to outside the cell?
• A. Very little. The electrical gradient (-90mV) will push the $K^+$ back, and an equilibrium will be reached between the electrical and chemical gradients …an electrochemical equilibrium.

Generation of Resting Membrane Potential

• Ion Concentration (chemical) gradient established by ATP driven, $Na^+/K^+$ exchange pump
• Ion movement across membrane (via (leak) channels)
• Net charge movement
• Transmembrane potential difference
  • $K^+$ +ve ions into the cell make membrane potential go more +ve
  • +ve ions out of the cell make membrane potential go more -ve

Equilibrium Potential - The Nernst Equation

• The electrochemical gradient for a specific ion is the sum of its chemical and electrical gradients across the plasma membrane.
• The Equilibrium Potential (E) is the electrical potential necessary to balance a given ionic concentration gradient across the membrane so that the net movement of the ion is zero (described by The Nernst Equation).
• The Electrochemical equilibrium occurs when chemical gradient + electrical gradient = 0
• $E (volts) = \frac{RT}{zF} . log<em>e \frac{[ion]</em>{out}}{[ion]_{in}}$ (Nernst equation)
  • E = the equilibrium potential (Nernst potential)
  • R = gas constant,
  • T = temp,
  • F = Faraday constant
  • z = ion valence (e.g., +1 for $K^+$ and $Na^+$, -1 for $Cl^-$)

The Nernst Equation, ICF, and ECF [ion]

• In humans, ($37^oC$) the equation simplifies to:
• $E (mV) = \frac{61}{z} log<em>{10} \frac{[ion]</em>{out}}{[ion]_{in}} mV$
• Calculate E for K ($E_K$)
  • $E<em>K = 61 log</em>{10} \frac{[5 mM]}{[150 mM]} = -90 mV$
  • z = ion valence

What About Other Ions?

• There are many other types of ion channels, but $Na^+$ channels are the next most important, after $K^+$ channels, for membrane potential in neurons.
• You can use the Nernst equation to calculate the equilibrium potential for $Na^+$
  • $E_{Na} = 61 log \frac{[150 mM]}{[15 mM]} = +60 mV$
• RMP will be the combination of E of all ions present AFTER taking into account membrane permeability to those ions.
• So, in simplified terms, RMP in neurons will be the combination of $E<em>{Na}$ and $E</em>K$. BUT remember, at rest, membrane permeability (P) to $Na^+$ is much lower than to $K^+$, and so RMP is closer to $E<em>K$ than $E</em>{Na}$.

Membrane Potential

• The membrane potential is a compromise
• Vm is always closest to the equilibrium potential of the ion species to which the cell is most permeable!!
• At rest, $P<em>K>>P</em>{Na}$, therefore Vm close to $E_K$!!

Changes in Ion Permeability Alter Membrane Potential

• $P_{Na}$: depolarisation
• $P_K$: hyperpolarisation

Types of Gated Ion Channels

• Ligand-gated
• Voltage-gated
• Mechanically-gated

Rich Variety of Ion Channels

• Na leak channels
• Voltage-gated Na channels
• Mechanically-gated monovalent cation channels (Na & K)
• Ligand-gated K channels
• Etc., etc., etc.
• And note: some types of gated ion channels are normally open but are then closed by the gating stimulus.

Ion Channels Confer Functional Ability

• Synaptic input zone: …ligand-gated channels
• Output zone: …voltage gated Ca channels
• AP conduction zone: …voltage-gated Na channels

Electrical Signalling in Neurons

• Neurons use changes in Vm to achieve electrical signaling ….and those changes in Vm are due to changes in membrane ion permeability.
• There are two major types of electrical signals used by neurons:
  • Local (graded) potentials
  • Action potentials