Signalling in the nervous system

• Neurons are necessary in the nervous system as they ensure specificity of signal transmission and increase the speed of transmission
• Diffusion time increase quadratically with distance
• The Stokes-Einstein law states that the time taken for diffusion is proportional to the square of the distance travelled
• The cytoskeleton is important for signal transmission in the nervous system because:

  • Nucleation and catastrophe of microtubules permits movement of neurotransmitters along the axon
  • Mobilisation of synaptic vesicles within the synaptic terminal
• The growth cone is the part of the axon that extends from the cell body and is responsible for guiding the axon to the effector cell; therefore, synaptic transmission takes place here
• Synapses are junctions between neurons that allow the transmission of information.
• Membrane channels are needed as the lipid membrane presents an energy barrier to ion crossing
• The sodium-potassium ATPase pump exchanges 3 Na+ ions out of the cell for 2 K+ ions into the cell
• Equilibrium potential is when there is balance reached between the electric force and the concentration gradient for all ions across a membrane.
• Equilibrium potential is calculated using the Boltzmann distribution
• Boltzmann distribution requires:

  • Energy of a single molecule (kT)
  • The energy of the particles in both states
  • The number of particles in both states
• Boltzmann distribution leads to derivation of the Nernst equation
• Nernst equation describes the equilibrium potential for a specific ion across a biological membrane
• Nernst equation: Vm = RT/zF ln(Cout/Cin) where

  • Vm = equilibrium potential of the ion
  • R = ideal gas constant
  • T = temperature (in Kelvin)
  • z = valence of ion
  • F = Farraday constant
  • Cout = concentration of ion outside the membrane
  • Cin = concentration of ion inside the membrane
• A change in membrane potential is used by neurons to signal information. The change in potential can be graded or sharp; the sharp changes are called action potentials.
• Depolarisation = a decrease in the difference in electrical potential across a membrane, therefore the inside of the cell becomes more positive
• Depolarisation is caused by an excitatory signal
• Hyperpolarisation = an increase in the difference in electrical potential across a membrane, therefore the inside of the cell becomes more negative
• Hyperpolarisation is caused by inhibitory signals
• The space constant is the distance over which a change in membrane potential decreases to 37% of its original value in a neuron.
• Larger animals evolved to have myelin and action potentials to overcome the space constant.
• Myelin is formed of glial cells in the central nervous system and oligodendrocytes in the peripheral nervous system.
• Axon depolarisation can only occur in non-myelinated regions known as nodes of Ranvier, located between Schwann cells along the axon.
• The "jumping" of depolarisation between nodes of Ranvier is known as saltatory conduction.
• Myelination increases the space constant as the distance travelled by the action potential is spread out along the axon.
• The resting potential across the axon membrane is -70mV.
• Resting potential of the axon membrane is maintained by the voltage-independent leak channels being open at equilibrium. This allows continual efflux of K+ ions to maintain the resting potential of -70mV.
• At equilibrium potential, the voltage gated Na+ and K+ channels are closed.
• In response to an action potential, depolarisation takes place. The axon becomes more positively charged due to the increased rate of efflux of Na+ out of the axon via voltage-gated Na+ channels.
• Depolarisation is a positive feedback loop: the increased sodium permeability (caused by opening of Na+ channels) causes and increase in membrane depolarisation; in response to depolarisation, more Na+ channels open
• The all-or-none principle ensures that an action potential is only generated once a threshold of depolarisation is reached.
• The all-or-none principle guarantees that once an action potential is generated, it is always full size, to ensure no information is lost
• Once the depolarisation threshold has been reached, the axon depolarises to +40mV.
• Following depolarisation, the axon potential repolarises. This involves voltage-gated Na+ channel closure and activation of voltage-gated K+ channels.
• A refractory period takes place following depolarisation to ensure all voltage-gated Na+ channels are closed.
• The refractory period, together with the threshold, allows the coding of information via action potentials as frequency modulation. This means the frequency of the signals is what encodes information.
• Following the refractory period, both voltage-gated Na+ and K+ ion channels close and K+ leak channels are the only channels open, allowing efflux of K+ to restore the resting potential of -70mV
• Voltage-gated Na+ and K+ channels are responsible for signal transduction while the Na+/K+ ATPase channel is responsible for maintaining the resting potential along with K+ leak channels.
• Speed of action potential is increased by:

  • Myelination - jumping of action potential between nodes of Ranvier increases the space constant
  • Wider diameter - decreases resistance of signal transduction
  • Higher temperature
• The refractory period ensures that the signal is unidirectional and as no excitation can take place while the Na+ channels reset, it means each action potential is discrete