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Tail currents

  • Hodgkin-Huxley cannot explain this phenomenon
  • We can consider model of channel where the gate sare not statistically independent
  • Instead of looking at individual gates, consider the state of the channel as a whole
  • Each state has a conductance and gating charge
  • If n states and probability of being in that state [math]\displaystyle{ Pr[\tilde{s}=s_n]=x }[/math],
    • [math]\displaystyle{ g=E[\tilde{g}]=\Sigma \gamma_nx_n }[/math]
  • Multiple channel state model with single conducting state can explain S-shaped onset of activating factor and also inactivating factors
    • The slow onset is due to the intermediate states that the channel has to go through to become conducting
    • Inactivation is explained by intermediate states which are more favorable to go away from that state

Sodium channel structure

  • 6 transmembrane domains
    • S4 has lots of charge and mutating removes voltage gating
  • Mutagenesis
    • 2 amino acid mutations can convert specificity away from Na to Ca
    • can mutate to eliminate inactivation