Ion channels

Ion channels

1. transmembrane pore forming proteins that allow passage of ions in/out of cell

   • characterisations
     • selectivity for particular ion species
       • size of pore
       • nature of channel lining
     • gating properties
     • sequence similarity/ molecular architecture/structure
   • main ions
     • cations = Na+, K+, Ca2+
     • anions = Cl-

2. Ion channel gating

   • voltage gated
     • underlie mechanism of membrane excitability
     • Na+, K+, Ca2+ selective channels
   • ligand gated
     • activated following binding of ligand to channel protein
     • channels which fast NT act
       • GABA = example
   • receptor operated
     • opened in response to hormones/drug acting on other cell membrane receptors
     • intracellular mediator
     • slow acting
   • others = pH gated, mechanically gated

3. excitable cell

   • generate change in membrane potential
     • AP produced
       • neurones, muscle cells
     • membrane pumps that allow maintence of cells resting potential
       • K+ leak channels
       • Ca2+ ATPase pump
       • Na+/Ca2+ leak channels
       • Na+/Ca2+ exchange
       • 3Na+/2K+ pump
       • 3 states that voltage dependent channels exist
         • closed (normal, resting)
         • open/activated (ions can move)
         • inactivated (ball and chain)
         • K+, Na+, Ca2+ voltage gated channels
           • K+ = hyperpolarisation of cells
           • Na+ = AP initiation
             • structure
               • 4 subunits
               • 6 membrane spanning regions
           • Ca2+ = muscle contraction, NT release

4. TRPs

   • transient receptor potential channels
   • metabotrophic receptor
   • activated by 2nd messengers
   • non selective cation channels that gate Na+ and Ca2+
   • 6 membrane spanning helices

5. Functional types of channels

   • K+
     • voltage gated
     • inwardly rectifying - allow entry more readily
     • 2 pore domain repolarising influence opposing excitation
     • agonists
       • can treat hypertension and angina
       • Examples = Pinacidil/Moxadil
     • antagonists
       • TEA/4AP
         • stimulate NT release
       • sulphonylureas
   • Na+
     • voltage gated
       • antagonist - neurotoxin and LA
     • receptor operated
       • antagonist - specific hormone receptor
     • ligand gated
       • antagonist - conotoxin
   • Ca2+
     • voltage operated
       • L type, long lasting
     • store operated
       • plasma membrane of excitable/non excitable
     • intracellular calcium channels
       • ER/SR
         • 2nd messenger activation
     • channel blocking drugs
       • used to treat cardiac disease
         • examples = Verapamil/Nifedipine

6. Nicotinic Ach receptor structure

   • 5 subunits
   • 4 domains
   • 2 Ach binding sites
     • bound for channel to open