Sodium Ion Channels

Sodium Ion Channels

1. Sodium selective channels that contribute to the generation of nerve impulses

   • Voltage gated sodium channels
   • Ligand gated ion channels
     • Both can have their action modified by toxins such as CTX, TTX, STX

2. Structure (mammals)

   • One large alpha subunit
     • Contains the homologous domains (D1-4)
     • Transmembrane spanning segment (S1-6)
       • Positively charged S4 region acts as voltage sensor
     • Reentrant loops act as ion selectivity filter
   • One or two smaller beta subunits

3. Ion channel gates

   • Action depends on the charge across the memnrame
     • Activation gate
       • higher probability of opening when depolarisation occurs and increase Na+ permeability
       • 3-4 located on the S4 regions
       • At resting potential all act gates are closed. inactivation gate open
       • All act gates need to be open for the channel to be open
       • Gating mechanism unknown
         • S4 region could move outwards or rotate to open the pore
         • cytoplasmic end of S6 moves to open the pore
     • Inactivation gate
       • Higher probablity of closing when depolarisation occurs to decrease channel permeability

4. Channel states

   • Each VGSC acts independently and randomly, but depolarisation increases the probability of the channel opening
   • If enough channels are open and a certain threshold is reached, it will generate an AP
   • During an AP, only some channels are open, others may stay closed or open more than once
   • In the inactivation state, they cannot open in response to depolarisation until the return to the closed state; neuron refractory
   • Neurotoxins alter the state of the channel, and therefore membrane potential and neurone function

5. Neurotoxin receptor sites

   • TTX binds at activation gate
   • CTX binds at inactivation gate

6. Neurotoxin resistence

   • (Bricelj 2005) certain populations of the softshell clam Mya arenaria are resistant to PSP toxins
     • bioaccumulation of toxin
       • increased risk when they are eaten as they would before have been poisoned
   • STX/TTX resistance
     • STX/TTX assosiates with a few amino acids that form the outer pore loop
       • a single substitution (glutamic acid to aspartic acid) causes a 1000 fold decrease in affinity at the STX/TTX binding site.

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