Ion Channel Receptors

Ion Channel Receptors

1. Specialised Functions of Ion Channels

   • mediate generation, conduction and transmission of electrical signals in the nervous system
   • control the release of neurotransmitters and hormones
   • initiate muscle contraction
   • transfer small molecules between cells
   • mediate fluid transport in secretory cells
   • control motility and growth of migrating cells
   • Provide selective permeability properties important for various intracellular organelles
   • ion channels are responsible for heart beat, muscle contraction, hormone excretion, vision, olfaction, pain - most things

2. Drugs to Remember for Ion Channels Lecture: •Phenytoin •Diazepam •Phenobarbital •Flumazenil

   • Phenytoin is the oldest non-sedative anti-seizure agent. It binds to sodium channels, stabilizing them in the inactive state.
   • Flumazenil (BZD overdose treatment) - negative allosteric modulator of GABA
   • Phenobarbital is a barbiturate: Prolong inhibitory postsynaptic potential by increasing the mean chloride channel opening time increase pore opening duration) -hence the duration of GABA-induced cell membrane hyperpolarisation
   • Diazepam is a benzodiazepine. Benzodiazepines potentiate the inhibitory effects of GABA by increasing pore opening frequency throughout the CNS, resulting in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects.

3. Ion Channel Dysfunction

   • Such diseases as: Epilepsy, deafness, blindness, migraine, arrhythmia, deregulation of cognitive function

4. ions cannot diffuse across the hydrophobic phospholipid bilayer: ion channels provide a polar environment for diffusion / transport across the membrane.

   • channels: ions transport down the concentration gradient
   • pumps: ions are actively transported against the gradient - energy required
   • ion channels are selectively permeable to specific ions
     • ion channels are gated by: •Voltage across the cell membrane •Ligands •Phosphorylation •Mechanical stimulus (stretch)
       • un-gated is rare
       • voltage: membrane potential
       • Ligand: toxins such as botulin are ion channel blockers, Ion permeation could also be prevented by channel blockers. Phenytoin is the oldest non-sedative anti-seizure agent. It binds to sodium channels, stabilizing them in the inactive state.
         • GABAA regulate Cl- channels (ligand-gating)
           • GABAA LIGANDS The modulate GABA action Agonists: Bind to the active site (where GABA binds) Antagonists: Compete with GABA for binding and thereby inhibit its action Positive Allosteric Modulators: Bind to allosteric sites on the channel causing an indirect increase in Cl- conductance Negative Allosteric Modulators: Bind to an allosteric sites on the receptor causing an indirect decrease in Cl- conductance
       • mechanical detect stretch

5. GABA

   • It is one of the inhibitory neurotransmitter of CNS
     • GABAA regulate Cl- channels (ligand-gating)
     • GABAB are G-protein-coupled receptors (different class)