• have no natural ligand.
• open and close as a result of changes
in membrane potential produced as
electrical currents move through
biological systems.
• propagation of nerve impulse through
axons, muscle contraction, and cardiac
function.
1. Stimulus above the gating threshold → channel opening Rapid
2. Depolarization caused by ion flow through the channel → hyperpolarization
and closing of the inactivation gate.
3. The inactivation gate remains closed until the membrane potential is reset by
the action of opposing forces.
4. Stimulation of the channel will not evoke a response until this “refractory
period” has ended and the resting potential (−50 to−70 millivolts) is restored.
electrical gradients across cellular barriers
result from differences in ion concentrations on the inside and
outside of cells created by the selective movement of ions across the
cellular barrier
•Mediate the 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 (gap
junctions)
• Mediate fluid transport in secretory cells
• Control motility of growing and migrating cells
• Provide selective permeability properties
important for various intracellular organelles
•let ions diffuse across the hydrophobic barrier of the lipid bilayer
• nicotine in tobacco is an agonist of nAChR, gives activation of reward system of brain
• smoking cessation medication Chantix is a partial agonist of nAChR and provides the lower level of channel activity upon binding than nicotine
• Chantix competes with nicotine for binding to nAChR
• Chantix decreases cravings and pleasurable effects of nicotine
membrane potential becomes more negative at a particular spot on the neuron’s
membrane
• open-close mechanism
• gating of a channel can be dependent on the presence of a ligand, environmental pH, temperature, or membrane voltage differences
• activated in the presence of a ligand
• close in the absence of a ligand
• Binding of ligand to channel causes conformational changes that causes the channel to open
• suitable ions migrate through channel
• ligand removed channel closes ion-flow stops
• can be activated by synthetic lens are blocked with antagonists(compounds that bind to the ligand binding side but do not lead to channel opening)
Not possible with agonists and
antagonists
• Options- Blocking the open channel directly
• E.g. Flecainide blocks Nav1.5, a
voltage-gated sodium channel that plays a major role in cardiac function, and is useful for the treatment of
arrhythmia and the prevention of tachycardia.
• The scorpion venom Margatoxinblocks the Kv1.3 channel, a voltage-
gated potassium channel found in a variety of cell types, including neuronal cells. Kv1.3 channel
blockade also can induce
immunosuppression by decreasing T-
cell proliferation.
•Either close or open state maintained
• Interaction of compounds with the protein at sites other than the
pore region. This could be considered a form of allosteric modulation,
as the “active site” of an ion channel is the pore through which ions
move.
• Retigabine, an anticonvulsant useful for the treatment of epilepsy and
seizures, stabilizes the open forms of voltage-gated potassium
channels Kv7.2 and Kv7.3, leading to increased potassium flow and
seizure suppression.
Contains over 3100 crystal structures categorised as iron
Amiodarone
•Used to treat cardiac arrhythmias prolonging the repolarisation
Down
• in the resting state voltage-gated channels are closed
• when membrane potential reaches the proper level conformational changes cause the channel to open
• ions flow across the membrane
• hyperpolarised state
• another set of conformational changes that inactivate the channel are induce
• channel cannot be opened until the resting potential is restored and it’s confirmation shifts back to the close resting potential state
Ion channels have… to:
Cation permeable:
Na+
K+
Ca++
Anion permeable:
Cl-
• Temperature-gated channels
• Mechanosensitive ion channels
• pH gating has also been observed
• Phosphorylation
• GPCR mediated
•Nicotinic acetylcholine receptor activated in the presence of acetylcholine
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