Neurophysiology — Axonal Conduction

Resting Membrane Potential

• Defined as the steady state potential difference (measured in mV) that exists across the cell membrane when the cell is in an unexcited state
• RMP of different excitable tissues varies → due to differing ionic permeability of the
  membrane (Ie. opening states of membrane ion channels) in the respective tissues at rest

Myelinated axon: -70 mV
Skeletal muscle cell: – 80 mV
Ventricular myocyte: – 90 mV
Cardiac pacemaker cell: – 60 mV

How is the membrane potential produced?

RMP is generated by uneven distribution of charged particles (i.e. ions and proteins) across the cell membrane 2^o to:

• Semi permeable membrane / selective membrane permeability to different ions
  At rest CM is:
  • Slightly permeable to Na: Na channels closed
  • Very permeable to K: open K+ leak channels → K down conc gradient from ICP to ECF
  • Variable permeability to Cl based on cell type
• Different ionic concentrations of ICF and ECF
  • Na+: 140mmol/L ECF; 20mmol/L ICF
  • K+: 150mmol/L ICF; 5mmol/L ECF
  • Na/K ATPase: 3Na+ out for 2K+ in. Consequences:
    • Osmotic effect: ↑ ECF [Na+] balances osmotic effect of ↑intracellular conc of –vely charged protein
    • Electrogenic effect: cell interior hyperpolarised
• Gibbs Donnan effect
  • Minor contribution to RMP
  • unequal distribution of large –vely charged protein impermeable to CM → affects distribution of other diffusible ions (K, Cl) and hence RMP by ~-10mV
    Principles

Principles

• Nernst equation
  • Nerst potential: voltage difference generated by EC gradient of an ion across CM (assuming complete permeability) i.e. contribution that a single ion makes to RMP
  • Calculated from valency, conc difference across membrane, and temp
  • The ion with ↑ membrane permeability → Nerst potential has ↑ contribution to total RMP
  • Nernst applied:
    • RMP has ↑ K permeability → net efflux of +vely charged K down conc gradient
    • drives membrane potential towards Nernst potential for K+
    • RMP ↓ permeability to Na+ ions
    • Therefore: measured neuronal RMP (-70mM) = close to Nernst potential for K+
• Goldman –Hodgkin-Katz equation
  • considers all ionic permeabilities and concentrations → RMP more precisely quantified
• Gibbs Donnan effect

Action Potentials

“Action Potential” (AP) → large rapid change in membrane potential that occurs in excitable cells

• AP = electrical response of neurons and other excitable tissues during which membrane potential rapidly ↑ and ↓
• All or nothing phenomenon
• Allow rapid signalling within excitable cells over long distances
• AP results from brief ↑ in membrane conductance to Na+, followed by slower ↑ in membrane conductance to K+
• Key parameters
  • RMP -70mV
  • Threshold potential -55mV
  • Peak potential (depolarisation) +20-40mV
  • Duration of AP 1-2ms

Events of an AP:

• Phase 1 – threshold potential: depolarisation stimulus reaches neuron → CM reaches -55mV → activation of voltage gated Na+ channels → Na+ influx > K+ efflux
• Phase 2 – AP: rapid influx of Na → further depolarisation → +ve feedback → rapid upstroke → drives membrane potential to Nernst potential for Na of ~+50mV → peak potential +30mV
• Phase 3 – repolarisation: AP never reaches theoretical max (+50mV) due to 2 events:
  • Inactivation of voltage gated Na+
    channels → ↓ membrane permeability to Na+
  • Delayed activation of voltage gated K+
    channels: ↑ membrane K+ permeability → K+
    efflux → membrane potential driven back towards Nernst for K+ of ~-90mV
  • Membrane potential briefly more –ve than RMP = “after hyperpolarisation” – due to gradual closure of voltage-gated K+
    channels
• Phase 4 – restoration of RMP
  • -70mV maintained by: Na/K ATPase (EC gradient) + Na/K pump

Saltatory conduction

• Saltatory conduction: propagation of AP along myelinated axons, whereby wave of depolarisation “jumps” from one rode of Ranvier to the next
• Mechanism of saltatory conduction
  • Depolarisation of a node → influx of Na ions → creating a sink (area of –ve charge at the surface)
  • +ve charge on nodes ahead flows into sink → ↓ polarity inside the membrane → AP → propagating current activates fast Na channels → wave of
    depolarisation down axon
  • minimal electrical signal degradation as axon is insulated by myelin sheath
  • AP reaches next node of Ranvier → continues down myelinated fibre
  • Nerve impulses appear to rapidly jump from one node to the next

Factors affecting Velocity of conduction

Velocity of conduction dependent on several factors:

• Nerve fibre myelination: AP propogation slow in Unmyelinated fibres
• Axon diameter: ↓ diameter → ↑ resistance to flow → ↓ conduction velocity
• Transmembrane resistance: ↓ resistance → ↑ loss of current flow → ↓ conduction
• Membrane capacitance: ↑ capacitance → longer to alter polarity → ↓ speed of propagation.
• Temperature: ↓ temp → ↓ rate Na+ channel opening → ↓ velocity
• Hyponatremia: ↓ Na+ conc gradient → ↓ velocity
• Hypermagnesemia: → ↓ ACh release → ↓ velocity
• acidosis → ↓ velocity

Bianca / Kerr 2016

Answer by Bianca, Kerr