Physiology 3140A Lecture Notes - Lecture 12: Transmembrane Domain, Potassium Channel, Neuromuscular Junction
2 May 2018
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Physiology 3140 Lecture 12
October 6 2017
MOLECULAR STRUCTURE OF IONS
- Ion channel components: subunits and domains
- Structure of subunit/domain
- Functional roles of each subunit/domain
- NOTE:
o Voltage gated channel: 4 units (tetramer)
o Transmitter gated channel: 5 units (pentramer)
o Gap junction/hemi channel: 6 units (hexamer)
o SOME EXCEPTIONS
▪ Other channels show voltage sensitivity as well
- The middle of the pore, the tetrameric vs hexametric, the area of the pore is larger as the number of
subunits increases
o Gap junction channel is larger than a voltage gated channel
Molecular structure of nicotinic AChR
- It is in the neuromuscular junction
- Two alpha subunits containing binding pockets for acetylcholine
- Ligand gated binding channel; TWO ACH bind to open the channel
o REQUIRES TWO LIGANDS
- Total = 2 beta, 2 alpha, 1 delta, 1 gamma
- HETEROMERIC CHANNEL
- Each single subunit shares similar topology
o Each subunit has four transmembrane domains where the N and C terminals are on the
extracellular side
o Transmembrane domain formed by alpha helical structures
o Four transmembrane domains; M1-M4
- TM2 (M2) of each subunit contributes the pore lining region
o It is important because it lines the inner lining of the pore
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Selectivity filter and gating of nAChR
- Have negatively charged residues from the both the inner and outer part of the pore
- When you have a negative charge near the pore, it repels anions away from the pore; anions can not
pass through the nACh receptors
o The channel only allows cations to flow through
o They have NO specification for the cation; NOT SELECTIVE to different species of cations
▪ Cations = Na, K, Ca, etc.
- NON SELECTIVE CATION CHANNEL
- Cross section of the area, there is a subtle changes in the M2 (lining the pore)
o Subtle rotations of M2 will put the channel in open or close positions
o MINOR changes required to open the channel
o Makes conformational changes to the gating area
Voltage-gated K+ channels are tetramers
- 4 subunits assemble to form the functional channel
o Tetrameric
- Each subunit is comprised of 6 membrane spanning domains, with cytoplasmic amino- and carboxy-
terminal regions
o Membrane segments = membrane spanning domain
▪ S1-S6
- If you had the whole channel, it is arranged in a way, where you can see each membrane segments
relative locations
- There is a pore loop forming the inner lining of the pore
o The two domains, S5+S6, are partially lining the pore
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find more resources at oneclass.com
Some structural features of K+ channels
- The S4 segment is full of charges and represents the voltage-sensor region
o Has positive charges residues in this region
o Forms the voltage sensor of the potassium channel
- The pore loop contains the selectivity filter, and is also the site for binding of various blockers
o E.g. TEA; tetra ethyl ammonium
o Pore loop = H5 area
o Pore blockers = stuck in the pore and block the channel from conducting ions
Ion selectivity
- Carbonyl oxygens on peptide chain in the region of the selectivity filter replace water and stabilize
each ion as it passes through the pore
- Potassium can easily go into the selectivity filter, because the energy required to dehydrate the
potassium is similar level when they interact with the carbonyl oxygen
o Note: potassium is hydrated when it enters the vestibular area
- The smaller sodium ions, can only interact with two of the carbonyl oxygen groups in the selectivity
filter
o They are in the higher energy state when entering the selectivity filter
o Tendency of the sodium ions, is to get out of the filter rather than go in
- The selectivity filter has MANY layers: THREE
- Potassium is going in easily and can move along the filter, and leaving the cell
o Interacts with the carbonyl oxygen groups
- Sodium can not go through. It is already in high energy state, it cannot go to the next level
o Just because sodium is smaller, it dos not mean that it is easier for it to flow through the
channel
o The channels accommodate the size of the specific ion
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Note: voltage gated channel: 4 units (tetramer, transmitter gated channel: 5 units (pentramer, gap junction/hemi channel: 6 units (hexamer, some exceptions, other channels show voltage sensitivity as well. The middle of the pore, the tetrameric vs hexametric, the area of the pore is larger as the number of subunits increases: gap junction channel is larger than a voltage gated channel. Two alpha subunits containing binding pockets for acetylcholine. Ligand gated binding channel; two ach bind to open the channel: requires two ligands. Total = 2 beta, 2 alpha, 1 delta, 1 gamma. Each single subunit shares similar topology: each subunit has four transmembrane domains where the n and c terminals are on the extracellular side, transmembrane domain formed by alpha helical structures, four transmembrane domains; m1-m4. Tm2 (m2) of each subunit contributes the pore lining region. It is important because it lines the inner lining of the pore.
