Physiol-01B5: Describe the structure and function of voltage sensitive ion channels.

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Structure of voltage-gated ion channels:

- Voltage-gated ion channels are transmembrane spanning proteins that consist of multiple
subunits (usually a tetramer, with each domain possessing 6 membrane-spaning α-helices)
surrounding a central pore (which permits ion selectivity based upon its specific size and
electrostatic charge)
- There is a “gating” mechanism involving a +vely charged voltage-sensing helix (S4
domain) that moves outwards only when the surrounding membrane environment is
depolarised

- As a result, there are three states in which the ion channel can exist, depending on the
state of the “gating” mechanism:
o (i) Opened state – A change in membrane potential (or voltage) leads to a
conformation change in the channel’s subunits (due to opening of the “gating”
mechanism) that result in opening of the central pore. This permits specific ions
to traverse the membrane down its electrochemical gradient, thereby altering the
ion conductance across the membrane
o (ii) Closed state – Pore is closed (due to inactivity of the “gating” mechanism
when is no change in membrane potential) and there is no ion flux across the
membrane
o (iii) Inactive state – Channel remains in a closed state and cannot be opened again
irrespective of changes in the membrane potential (Nb. this forms the basis of the
“refractory period”)

Function of voltage-gated ion channels:

- Fast VG-Na+ channels
o Found in nerve and muscle cells – Involved in depolarisation and AP
transmission
- Delayed rectifier K+ channels
o Found in nerve and muscle cells – Involved in repolarisation
- VG-Ca2+ channels
o Two types – T and L types
o Found in cardiac and skeletal muscle, pacemaker cells, and nerve cells – Involved
in vesicular exocytosis (Eg. NT release), excitation-contraction coupling, cardiac
action potential (phase 2), and automaticity