Week 6: Ion channels

Week 6: Ion channels

1. Ligand gated ion channels

   • nAChr channels - excitatory Na+, little K+
   • GABA a receptors - inhibitory Cl- channels
   • Glycine receptors - inhibitory Cl- channels
   • 5 HT3 receptors - excitatory Na+ channels
   • Ionotropic glutamate receptors
     • NMDA receptors excitatory: Na+, K+ and Ca2+
     • Kainate receptors excitatory: Na+, K+
     • AMPA receptors excitatory: Na+ K+
   • P2x receptors - excitatory Na+

2. Nicotinic receptor

   • mediated effects of Ach released from motor endplate onto skeletal muscle fibres
   • Permeable to Na+ ions
   • ACh binds to receptor, channels opens Na+ ions flow into cell
   • Nicotinic receptor is made up of 5 subunits

3. How do ligand gated ion channels work

   • Transmitter do not bind irreversibly - bind and release until broken down in synaptic cleft
   • Higher transmitter concentration in cleft; greater the overall proportion of receptors occupied at any one moment
   • Receptor binding doesn't simply switch channel to open position for duration of binding
   • Receptor binding increases open probability of channel or its mean duration of opening

4. GABA a receptor activation

   • Action potential depolarises terminal Ca2+ enters vesicles fuse and GABA is released
   • GABA binds to post synaptic GABA receptors, channels opens Cl- ions pass through hypoerpolarising post synaptic cell

5. Ligand gated ion channels can be modulated

   • Allosteric modulators do not bind to same site as GABA, nor do they open the channel themselves

6. Voltage-gated sodium channel

   • Major protein alpha is encoded by single gene
   • 4 subunits, each with similar 6 transmembrane domains
   • Similar structure to voltage gated sodium channels
   • 4 functional types of voltage ca2+ channels can be distinguished

7. Na and Ca2+ channel drugs

   • Lidocaine - local anaethetic works by blocking voltage sensitive Na+ channels
   • Tetrodotoxin - puffer fish is irreverisble blocker of voltage sensitive na+ channels
   • Ziconotide is peptide from Cone shells that blocks N-type voltage gated Ca2+ channels

8. Potassium channels

   • K+ channels are most ubiquitous channel type
   • Voltage sensitive K channels
   • Calcium sensitive K+ Channel
   • Tandem pore domain channels
   • Inwardly rectifying K+ Channels

9. TRPv1 channels

   • Active ingredient is capsaicn
   • non-selective cation channel - passes Ca2+, Na+, K+
   • 6 trans membrane domains
   • Phosphorylation changes its opening/closing characteristics
   • Powerfully influences the excitability of nociceptors to mechanical and chemical stimuli in the body
   • Sensitises nociceptors during inflammation/damage to protect healing tissue

10. Ion channels properties and amino acid sequence

    • Channel is highly selective for Cl- ions
    • Mutations of ion channels can cause disorders 'channelopathies'
      • 5CN9a is human gene encoding the major component of the voltage sensitive Na+ channel

11. Ion channel reversal potentials

    • Nicotinic ion channels are permeable mostly to Na+ with a little K+ and Ca2+ and drive membrane potential towards +5mV

12. Synaptic 'reversal potential'

    • Releasing ACh onto nicotonic receptors on muscle cells
    • EJP changes size when muslce is held, which affects driving force for Na+ ions