Ion channels

Ion channels

1. Ion channels

   • Fast (10^8 ions/s)
   • Direction down a concentration gradient

2. Ion pumps

   • Transporters (like a ferry)
   • Slower (10^5 ions/s)
   • Move ions 'uphill' (against energy barrier)
   • e.g. Na+/K+ ATPase

3. Properties of voltage-dependent ion channels

   • Detect voltage (membrane potential)
   • Specificity for Na+ or K+
   • Inactivation mechanism

4. Voltage-dependent Na+ channel

   • Structure
     • alpha, beta1 & 2 subunits
   • How does the channel know when to open?
     • Voltage sensor S4
       • 4th transmembrane domain is the voltage sensor
     • Positively charged amino acids (Arg, Lys) conserved in S4 of different channel proteins
     • Line up on outside of the S4 alpha helix - respond to depolarisation by 'moving' towards outside
     • As neuron is depolarised, inside is more positive and voltage sensor moves to create gating current
       • This movement causes conformational change and channel opening
   • Selectivity filter
     • Does not have the signature sequence of K+ channels
     • The Na+ channel selectivity filter is WIDER than in K+ channels
     • Hydrated Na+ ions can pass through filter
     • A. K+ could fit through the narrow portion of the Na+ channel pore with a complete hydration shell if it was uncharged (no glutamate present in channel)
     • B. In the presence of the charged glutamate residues K+ cannot do so with the geometry preferred, as this involved water molecules bridging between the ion and the nearby glutamate side chains
     • C. In contrast, the smaller Na+ ion can fit through the pore with the preferred geometry, while retaining some of its hydration shell

5. Ion selectivity

   • Why don't Na+ pass through K+ channels
   • Ions have hydration shells
   • Na+ = 0.95A
   • K+ = 1.35A

6. Voltage-dependent K+ channel

   • Tetramer
   • Oxygens in the protein replace the oxygens of water from the hydration shell
   • Estimated that 2 K+ can travel through channel at one time
   • OH comes from the peptide bond
   • Na+ cannot pass through even though it is small because it would disrupt its hydration shell, thus is thermodynamically unfavourable
   • Conserved glycine in the inner helix allows a 'kink'/hinge and gate opening