Neurophysiology

• Excitability


  Through ion channels and ionic gradients
• Gradient


  Property of the cell membrane and the internal and external environment, typically electrochemical - chemical concentration gradient but an electrical gradient as well (charge differences across the membrane; capacitance - ability to 'store' charge)

  
• Ion channels


  Allow current flow, if an ion channel opens, ions (current) can flow across a membrane
• Ion channels


  • Membrane proteins with properties of enzymes (environment must be correct etc)
  • Can be highly selective, but not always
  • Can be 'modulated'
  • Can activate, deactivate and inactivate (but don't always do all those things)
  • May be receptor proteins
  • Transport is 'passive', but involves a gradient
• Equilibrium potential


  The point at which an ion reaches equilibrium and the 'driving force' for the ion stops
• Calculating equilibrium potentials


  Using the Nernst equation: EmV = 61.5* x log10 [ion]out / [ion]in
• All cells have a membrane potential
• Membrane potential


  Predicted by the Goldman (GHK) equation, which for the 3 main permeant ions under physiological conditions is: Em = (RT/F) ln [(PK[K+]o + PNa[Na+]o + PCa[Ca2+]o)/(PK[K+]i + PNa[Na+]i + PCa[Ca2+]i)]

  
• Gated channels


  • Ligand-gated, e.g. acetylcholine receptor, NMDA-receptor
  • Voltage-gated, e.g. Na+ and K+ channels in nerve cell membrane
• States of the sodium channel

  1. Resting/deactive

  2. Activated after initiation of AP

  3. Inactivation - quite rapid

  4. Absolute 'refractory period' - ions cannot pass
• Stages of the nerve (nodal) action potential

  1. Membrane at rest

  2. Depolarisation

  3. Repolarisation

  4. No net flow
• Action potentials are not only important in nerves, but also in muscle - skeletal, cardiac, smooth
• Stages of the myocyte action potential

  1. Phase 4: Resting membrane potential, largely determined by permeability to K+

  2. Phase 0: Activation of voltage-gated Na+ channels, inward current moves Vm towards ENa

  3. Phase 1: Early repolarisation due largely to inactivation of Na+ channels

  4. Phase 2: 'Plateau' phase; inward current through slowly activating and inactivating voltage-gated Ca++ channels

  5. Phase 3: Repolarisation phase; inactivation of Ca++ channels and increase in permeability to K+

  
• Shape, size and duration of the action potential are different in different parts of the heart
• Injection of a bolus of KCl


  May lead to heart failure
• Initiating an action potential in a nerve

  1. Triggers a further event, and/or propagates down a nerve - at the same size and shape

  2. Usually initiated at the 'axon hillock'

  3. Requires some form of stimulation or receptor event on the membrane
• Propagation of the action potential

  • Depends on size of axon, and how 'leaky' it is
  • Wide axons are less resistant and if there are less leaks, allows wave of depolarisation to move ahead further
  • Myelination allows increase in speed in same size neurone
• Speed of the action potential propagation is rapid