Transmitters and excitability

Transmitters and excitability

1. Development of excitability

   • Resting potential falls during development
     • New channels, new pumps
     • Glia (astrocytes) ↑, [K+]o ↓ ~35mM to ~3mM
   • Action potentials appear early
     • e.g. Xenopus – from closure neural tube
   • Different ways to develop excitability
     • Go back to lecture and find images

2. Action potential development

   • Two principal routes:
     • Long, Ca2+-dependent then short, Na+-dependent
       • tetrodotoxin-resistant
       • e.g. mouse dorsal root ganglion, Rohon-Beard cells
         • Rohon-beard cells
           • Mechanosensory cells of lower vertebrate dorsal spinal cord
           • Appearance of delayed rectifier K+ channel (Kd) important
     • Short Na+-dependent
       • e.g. mouse spinal cord

3. Delayed rectifiers

   • A rectifier is a channel that only allows current (ions) through one way
     • Appearance of such channels shortens the ap
       • Na+ currents also increase in Xenopus.
   • A delayed rectifier is a channel that opens some time after its voltage threshold has been reached

4. Calcium waves

   • Waves influence process growth
   • Waves influence differentiation
     • e.g. Xenopus, expression of GABA

5. Receptor development

   • Neuronal development involves changes in receptor
     • Populations
     • Subunits
     • Localisation
     • Efficacy
   • GABA receptor development
     • What do adult GABA receptors do?
       • Adult GABA receptors inhibitory
         • GABAA ionotropic
         • GABAB metabotropic
     • In development GABAA depolarize
       • immature neurons have ↑ [Cl-]i
         • Cl- efflux causes Na+ and Ca2+ influx via VAC’s
       • ↑ expression of K+ / Cl - co-transporter KCC2 (out)
       • ↓ decreased expression NKCC1 (in)
         • Switches effect to hyperpolarizing
     • Receptor subunits change
       • e.g. GABAAα
   • NMDA receptor development
     • N-methyl-D-aspartate (NMDA) receptor
     • NR1 (8 forms) + 4 NR2
     • variable composition and properties
       • e.g. developmentally-regulated Mg2+ block
       • e.g. cortical neurons in vitro
         • change in subunit expression
         • change in antagonist effects

6. Key points

   • Electrical activity develops
   • Ion populations, receptors, neurotransmitter roles and expression all change

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