Resting potentials and action potentials

Synergy between the body's various organs and tissues requires a high degree of coordination and rapid communication between cells across long distances. Communication between cells, or cell signaling, occurs by way of electrochemical signals transmitted by charged ions, the distribution of which along the cell membrane is subject to a sensitive balance. This is referred to as electrogenic transport, as opposed to electroneutral transport, which involves the transport of uncharged particles.

The distribution of charged ions along the cell membrane results in a disparity between the electrical potential on the inside of the cell and the space that surrounds it. This is referred to as membrane potential. In its quiescent state, the voltage difference across the cell membrane requires energy to uphold. This is referred to as resting potential. The transport of charged particles through the cell membrane leads to a change in potential along the membrane and forms the basis for the transmission of information. This is referred to as an action potential.

Overview

• Differences in the concentration of cations and anions inside and outside the cell lead to distinct membrane potentials (see also section on “Electrolytes” in laboratory medicine).
• Besides electrolytes, negatively charged particles (especially those within the cell) also affect charge distribution.
• The following table lists the concentrations of the most important intracellular and extracellular cations based on an idealized model of a neuron.

Basics of conduction

Ion solutions conduct electricity. The speed of ion transport is determined by the strength of the electric field. Electric field strength is determined by ionic strength, which is a measure of the concentration of ions and their charge in a solution.

• Membrane potential: a concentration gradient determined by the presence of positively and negatively charged ions across the plasma membrane (i.e., inside and outside of the cell) that results in a buildup of voltage (potential)
• Nernst equation
  • The equation determines the electric equilibrium potential of a cell membrane with respect to a specific type of ion.
  • Formula: E_ion = 60/z log [ion]_out/[ion]_in
    • E_ion = equilibrium potential
    • Z = absolute value of ionic charge
    • [Ion]_out = ion concentration outside cell
    • [Ion]_in = ion concentration inside cell
• Ion flux: the rate of ion flow across the plasma membrane
  • Dependent on the ability of ions to cross the membrane and the potential difference on both sides of the membrane, which acts as a driving force
  • Formula: J = Λ × ΔU
    • J = ion flux
    • Λ = membrane conductivity
    • ΔU = potential difference

Physical fundamentals of conduction

Basic principles

• Depolarization of the membrane: The influx of cations results in an increased positive charge on the inside of a cell.
• Electrotonic conduction
  • Depolarization of one area of the membrane automatically leads to the passive depolarization of neighboring areas.
  • This effect depends on membrane resistance and the shape of the electrical conductor (axon diameter). Describing electrotonic conduction requires consideration of these two aspects.

Physical laws governing nervous conduction along the cell membrane

The laws are based on cable theory.

Axial resistance (ri)

• Definition: resistance of cytosol to the forward movement of charged particles
• Formula: ri = ρ × l / A
  • r_i = resistance
  • ρ = specific resistance
  • l = length
  • A = surface of section
• Measure: Ω (ohm)
• Effect on conduction: The lower the axial resistance, the better and faster the conduction.
• Influence of nerve fiber thickness: The thicker a nerve fiber, the lower the axial resistance (Hagen-Poiseuille equation).

Membrane resistance (rM)

• Definition: resistance of the cell membrane to the passage of charge carriers
• Effect on conduction: The higher the membrane resistance, the better the conduction (as fewer charge carriers are lost).
• Influence of nerve fiber thickness: The thicker a nerve fiber, the lower the membrane resistance.

Membrane capacitance (CM)

• Definition: Membranes of nerve fibers function as a sort of capacitor and can take up a certain amount of electric charge that is not passed on.
• Effect on conduction: The higher the membrane capacitance, the worse the conduction.
• Influence of nerve fiber thickness: The thicker a nerve fiber, the greater the membrane capacitance (as this also entails an increase in the surface area of nerve fibers, on which voltage can build up).

Length constant (λ)

• Definition: A constant numerical value that quantifies the length that an electrical signal can travel along an axon before decaying.
• Effect on conduction: : The higher the length constant, the further an electrical signal can propagate before decaying.
• Influence of nerve fiber: The presence of myelin significantly increases the length constant.

Membrane resistance and capacitance are inversely related (the higher the resistance, the lower the capacitance).

Large myelinated fibers have longer length constants and a faster conduction velocity than thin unmyelinated fibers.

Demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis lead to increased membrane capacitance, decreased membrane resistance, decreased conduction velocity, and a decreased length constant.

Overview

• Resting potential (RP): the membrane potential of an excitable cell (e.g., a neuron or muscle cell) at rest.
  • Default state of the cell
  • Corresponds more or less to the sum of all diffusion potentials (i.e., potentials in dynamic equilibrium) of extracellular and intracellular ions.
  • Depends on the type of cell and can range from approx. -70 mV to -90 mV.
• Brownian motion: the random motion of particles that makes diffusion possible
• Semipermeable membrane: The availability of ion canals with selective transport allows K⁺ ions (in some cases also Cl^- ions) to pass easily through the cell membrane at a resting state and makes it more difficult for Na⁺ ions to pass through.

Na⁺/K⁺-ATPase

• Mechanism
  • The sodium-potassium pump is an active transport pump in the plasma membrane that maintains a cell's resting potential.
  • Hydrolysis of one ATP molecule on the cytosolic side of the pump → efflux of 3 Na⁺ molecules and influx of 2 K⁺ molecules .
• Inhibitors
  • Na⁺/K⁺-ATPase is directly inhibited by cardiac glycosides (e.g., digoxin and digitoxin) → indirect inhibition of Na⁺/Ca²⁺ exchange → ↑ intracellular Ca²⁺ concentration → ↑ cardiac contractility
  • Ouabain inhibits the potassium-binding site on the Na⁺/K⁺-ATPases.
• Ion distribution
  • Intracellular molecules: K⁺, proteins (have a negative charge)
  • Extracellular molecules: Na⁺, Ca²⁺, Cl^-

The RP corresponds more or less to the K⁺ equilibrium potential, which varies according to the ion channels present in the cell: neurons ≈ -70 mV, myocytes (skeletal and cardiac) ≈ -90 mV, glial cells ≈ -90 mV.

To remember the direction of the ion transport regulated by Na⁺/K⁺-ATPase, think: “Kome in!” (K⁺ goes inside the cell).

An action potential (AP) is a sequence of changes in the voltage-gated ion channels in a neuronal cell membrane that generate a nerve impulse.

Phases

Uncontrolled ion flow that is solely due to depletion of the concentration gradient is known as a leak current.

Duration of action potentials

The duration of an action potential is dependent on cell type.

Control of action potentials

The membrane potential reached during depolarization does not reflect the stimulus intensity. Electrochemical impulse conduction is subject to the all-or-none principle: depolarization of the membrane is either triggered by an action potential or not. The stimulus intensity is only evident in the frequency of consecutive action potentials that follow.

• Stimulus intensity in relation to voltage
  • Threshold potential: measure of potential difference using the net charges on both sides of the cell membrane
    • Approx. -50 mV
    • Potential that must be reached for an action potential to be triggered
    • If it is exceeded, all voltage-dependent Na⁺ channels are activated and an action potential occurs.
• Stimulus intensity in relation to current strength
  • Rheobase: minimum current amplitude required for an action potential
  • Chronaxie: minimum time required for a current twice the strength of the rheobase to trigger an action potential

Conduction of action potentials

The occurrence of an action potential through the opening of the ion channels and the resulting depolarization are local events. In order for an action potential to function as an impulse for communication, it must be directed, i.e., passed on in one direction. Neural backpropagation is usually prevented by the refractory period of the responsible Na⁺ channels. Stimulus conduction either ensues rapidly (along the myelinated nerve fibers via saltatory conduction) or slowly along the non-myelinated nerve fibers via continuous conduction.

• Continuous conduction: slow conduction of an impulse along a non-myelinated nerve fiber
  • Triggering of an action potential: at an arbitrary area of the membrane where the threshold potential is exceeded
  • Transmission of an action potential: Depolarization of the membrane ensures the opening of voltage-dependent Na⁺ channels in adjacent areas (depolarization migrates along the cell membrane).
• Saltatory conduction: fast conduction of an impulse along the axons of myelinated nerve fibers
  • Triggering of an action potential: only at non-myelinated areas of the membrane (nodes of Ranvier) where the threshold potential is exceeded
  • Transmission of an action potential: Depolarization of a node of Ranvier leads to the opening of voltage-dependent Na⁺ channels at the next node of Ranvier (depolarization skips along the cell membrane).
    • Two factors promote depolarization of the adjacent node of Ranvier:
      1. Shifts in the adjacent charge carriers lead to changes in the potential field.
      2. The insulation of certain areas of the membrane (internodes) prevents the passage of charges and in this way enables a continuous ion current to the next node of Ranvier.

The transfer speed along a nerve is above all dependent on the electrical insulation provided by myelin sheaths: The thicker the myelin sheath, the faster the conduction of the stimulus!