Ion Channels

• GATING = the process by which ion channel opening and closing is controlled
• VOLTAGE-GATED = an ion channel whose opening and closing is controlled by membrane potential (depolarises)
• LIGAND-GATED = a channel whose opening and closing is controlled by the binding of a ligand
• ALPHA (α) SUBUNIT = the main pore-forming subunit of a voltage-gated ion channel
• PSEUDO-SUBUNITS = a structural component of a voltage-gated calcium/ sodium channel alpha subunit- they're linked into a continuous peptide chain
• SELECTIVITY FILTER = the part of the channel that determines which ions can pass through
• SELECTIVE PERMEABILITY = the tendency of an ion channel to only allow certain ion to pass through the channel's pore
• VOLTAGE SENSOR = a charged structure that in voltage gated ion channels in the fourth transmembrane domain of each subunit/ pseudo-subunit
• VOLTAGE GATED CHANNEL STRUCTURE AND FUNCTION

  • TETRAMERS = can be heterotramers or homotramers
  • transmembrane protein that crosses the membrane 6 times

  -->has 6 transmembrane domains- all alpha helices

  • the pore-forming subunit is the alpha subunit- consists of 4 copies of a voltage-gated potassium channel-like structure strung together into a single peptide

  -->each of these segments are called a pseudo subunit

  
• SELECTIVE PERMEABILITY

  • there are rings of charge in the voltage-gated potassium channel's selectivity filter

  -->ring of negative charge attracts cations, but repels anions

  • oxygen can be found lining the pore - to help stabilise the ion as it crosses the membrane

  1. selectivity filter strips off hydration shell from the ion
  2. ion moves into the channel
  3. knock-on mechanism: the entry of one ion into the channel pushes one of the other ions occupying the channel out the other side
• SELECTIVE PERMEABILITY cont.

  • potassium ions are just the right size to interact with the oxygen; the sodium ions are too small so cannot interact/ form bond with the oxygen
• HOW CHANNELS OPEN AND INACTIVATE

  • The voltage sensor has charges in it and if you put a charged substance in an electrical field and then charge the electrical field, that charged peptide will move

  1. as the membrane depolarises, the voltage sensor moves and pulls the channel open
  2. sodium ions can now cross the membrane
  3. as they cross the membrane, they'll start to increase the membrane potential (+ve)
  4. Ball-and-chain like structure swings up and blocks the mouth of the channel (inactivation gate)
• HOW CHANNELS OPEN AND INACTIVATE cont.

  • the inactivation particle in sodium channels appears to be in the linker between the third and fourth pseudo units
• CALCIUM CHANNEL FUNCTION SUBTYPES

  
• PHYSIOLOGICAL SIGNIFICANCE

  • Voltage gated sodium channels

  1. produce the excitatory phase of action potentials in neurone and skeletal muscle

  • voltage gated potassium channels

  1. help repolarise neurons and other cells during second phase of an action potential
  2. involved in inhibitor responses to many neurotransmitters

  • voltage gated calcium channels

  1. involved in excitatory phase of action potentials in cardiac muscle
  2. help trigger the vesicular release of neurotransmitters
  3. help couple electrical excitation of muscle contraction
• SIGNIFICANCE AS DRUG TARGETS

  • Drugs to treat high blood pressure =calcium channel blockers (e.g. verapamil + nifedipine)
  • Drugs to treat pain = local anaesthetics (lidocaine) and calcium channel blockers derived from marine snail toxin have been used to treat pain resistant to morphine
  • Drugs to treat heart rhythm disorders = calcium, sodium and potassium channel blockers and are all used to treat dysrhythmias
  • Drugs used to treat angina (severe heart pain caused by lack of oxygen supply to heart muscle) = verapamil + nifedipine are calcium channel blockers