Ion Channels PDF

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16.

TRANSPORTERS & ION CHANNELS II


1. ION CHANNELS VS. TRANSPORTERS
• Like some transporters, ion channels allow for the passage of ions down their
gradient by passive mechanism
• High selectivity/specificity for specific ions at very high rates
• Exhibit pores
• Forms an aqueous pore deep within

2. TYPES OF ION CHANNELS


• Many types of ion channels
• K+ channels: regulate membrane potential, AP recovery
o Membrane has high permeability of K+ due to the channel
• Na+ channels: Underlie AP
o Exists outside the cell, sodium ion moves into cell, change in
membrane potential
o The actual amount is very tiny, but this amount is enough to generate
an AP
• Ca2+ channels: ER and SR membrane to increase cytosolic concentration
and induce secretion
• Cl- channels: Regulate Ionic Balance (Membrane Potential)
• H+ channels: Rapidly increases intracellular pH (By kicking it out)
• Non-selective ion channels: Many functions

3. GENERAL PROPERTIES
• Lined by polar regions of the protein and is hydrophilic (oriented inside to form
the pore)
• Hydrophobic amino acid side chains interact the bilayer
• 4 identical subunits
• Stimulus (ligand, voltage) makes a conformational change in structure
o Produces an opening
• Gate is relied on conformational change
4. GATING OF ION CHANNELS
I. Voltage-Gated Channels
• Opening by change in membrane potential (depolarization/polarization)
• These channels are said to be voltage sensitive

II. Ligand-Gated (Extracellular) Channels


• Opening occurs because of binding of an extracellular ligand
(neurotransmitter)
• Ionotropic receptors

III. Ligand-Gated (Intracellular) Channels


• Channel gating is regulated by binding of an intracellular factor

IV. Mechanically Channel


• Mechanical stress or force opens the channels
5. SELECTIVITY
K+ Channel
• Highly conserved in prokaryotic and eukaryotic cells and represent an
excellent model for studying ion channels
• First structure of an ion channel was the KcsA K+
• This allowed us to understand the basic structure/function of ion channels

KcsA K+ Channel (27)


• Composed of 4 subunits (2 shown)
• Single polypeptide
• Forms a selective filter
• 5 rings of carbonyl oxygen forms stability for K+
The Selectivity Filter
• Structure of KscA channel reveals high selectivity for K+

• The selectivity filter is composed of 5 rings that has a diameter that


specifically accommodates for the atomic size of K+ but not Na+

• K+ must lose its hydration (shell of water molecules) before entering the filter
o K+ instead interacts with the carbonyl oxygen lining the filter instead of
the water molecule
o Since Na+ is smaller in atomic size, therefore is too far away to interact
with the oxygen molecules to compensate for the energy expense from
the losing the water molecules necessary before entering the filter.
o In other words, it is too energetically costly for the Na+ to enter the filter
6. IONIC BASIS OF MEMBRANE POTENTIAL
• Separation of charge between a barrier (Bilayer)
• Difference in charge is from movement of ions
• Voltage sensitive gating

Voltage Sensitivity (40)


• Transmembrane segments S1-S4 form the voltage sensor
• S4 helix (composed of positively charged amino acids) is the key component
• At rest, cell interior is negatively (-) charged, S4 is near the cytosol and the
channel is closed
• When the cell is depolarized (more +), the S4 is then pushed towards the now
more “negatively (-)” charged extracellular side, opening the gate
K+ Leaky Channels
• However, not all channels are voltage-gated
• These channels lack the voltage-sensitive transmembrane segments that
imparts voltage-sensitivity
• As a result, they are always open and set the resting membrane potential

Na+ Channels in Neurons

• Regulated by voltage (depolarization)


• Contributes to a significant change in Membrane Potential
• Continuous chain
• Sodium channel work quickly, allow for rapid change in MP
• Change in membrane potential, very soon after that change, that plug begins
to interact
• Sodium ions are no longer moving through
• Membrane to recover faster
• Inactivate gate is really for faster recovery.
• Cannot wait for the channel to close itself.
3 STATES: OPEN, INACTIVE, CLOSED
1. Cell is at rest with a negative membrane potential à Closed
2. Cell is depolarized à Open
3. The Inactivation Gate quickly plugs the channel pore à Inactivation
4. When the cell returns back to its Resting Membrane Potential, the gate
resets à Closed

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