Everything about Potassium Channel totally explained
In the field of
cell biology,
potassium channels are the most widely distributed type of
ion channel and are found in virtually all living organisms. They form
potassium-selective
pores that span
cell membranes. Furthermore potassium channels are found in most
cell types and control a wide variety of cell functions.
Function
In excitable cells such as
neurons, they shape
action potentials and set the
resting membrane potential.
By contributing to the regulation of the
action potential duration in
cardiac muscle, malfunction of potassium channels may cause life-threatening
arrhythmias.
They also regulate cellular processes such as the secretion of
hormones (
for example,
insulin release from
beta-cells in the
pancreas) so their malfunction can lead to diseases (such as
diabetes).
Types
There are four major classes of potassium channels:
The following table contains a comparison of the major classes of potassium channels with representative examples (for a complete list of channels within each class, see the respective class pages).
Structure
Potassium channels have a
tetrameric structure in which four identical protein
subunits associate to form a four fold
symmetric (
C4) complex arranged around a central ion conducting pore (for example, a homotetramer). Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C
4 symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability.
There are over 80
mammalian genes that encode potassium channel
subunits. However potassium channels found in
bacteria are amongst the most studied of ion channels, in terms of their molecular structure. Using
X-ray crystallography, profound insights have been gained into how potassium ions pass through these channels and why (smaller)
sodium ions don't (since sodium ions have greater
charge density, they've a larger shell of
water molecules surrounding them and thus are more bulky). The
2003 Nobel Prize for Chemistry was awarded to
Rod MacKinnon for his pioneering work in this area.
Selectivity filter
Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by five residues (TVGYG-in prokaryotic species) in the P loop from each subunit which have their electro-negative carbonyl oxygen atoms aligned towards the centre of the filter pore and form an anti-prism similar to a water solvating shell around each potassium binding site. The distance between the carbonyl oxygens and potassium ions in the binding sites of the selectivity filter is the same as between water oxygens in the first hydration shell and a potassium ion in water solution. Passage of sodium ions would be energetically unfavorable since the strong interactions between the filter and pore helix would prevent the channel from collapsing to the smaller sodium ion size. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue (Gly79 in KcsA). The next residue towards the extracellular side of the protein is the negatively charged Asp80 (KcsA). This residue together with the five filter residues form the pore that connects the water filled cavity in the centre of the protein with the extracellular solution.
The carbonyl oxygens are strongly electro-negative and cation attractive. The filter can accommodate potassium ions at 4 sites usually labelled S1 to S4 starting at the extracellular side. In addition one ion can bind in the cavity at a site called SC or one or more ions at the extracellular side at more or less well defined sites called S0 or Sext. Several different occupancies of these sites are possible. Since the X-ray structures are averages over many molecules, it is, however, not possible to deduce the actual occupancies directly from such a structure. In general, there's some disadvantage due to electrostatic repulsion to have two neighbouring sites occupied by ions. The mechanism for ion translocation in KcsA has been studied extensively by simulation techniques. A complete map of the free energies of the 2
4=16 states (characterised by the occupancy of the S1, S2, S3 and S4 sites) has been calculated with molecular dynamics simulations resulting in the prediction of an ion conduction mechanism in which the two doubly occupied states (S1, S3) and (S2, S4) play an essential role. The two extracellular states, S
ext and S
0, were found in a better resolved structure of KcsA at high potassium concentration. In free energy calculations the entire ionic pathway from the cavity, through the four filter sites out to S
0 and S
ext was covered in MD simulations. The amino acids sequence of the selectivity filter of potassium ion channels is conserved with the exception that an isoleucine residue in eukaryotic potassium ion channels often is substituted with a valine residue in prokaryotic channels.
Central Cavity
A 10 Å wide central pore is located near the center of the transmembrane channel where the energy barrier is highest for the transversing ion due to the hydrophobity of the channel wall. The water-filled cavity and the polar C-terminus of the pore helices ease the energetic barrier for the ion. Repulsion by preceding multiple potassium ions is thought to aid the throughput of the ions.
Blockers
Potassium channel blockers, such as
4-Aminopyridine and
3,4-Diaminopyridine, have been investigated for the treatment of conditions such as
multiple sclerosis.
Muscarinic potassium channel
See also G protein-coupled inwardly-rectifying potassium channel
Some types of potassium channels are activated by
muscarinic receptors and these are called
muscarinic potassium channels (I
KACh). These channels are a heterotetramer comprised of two
GIRK1 and two
GIRK4 subunits. Examples are potassium channels in the heart, which, when activated by
parasympathetic signals through
M2 muscarinic receptors, causes an outward current of potassium which slows down the
heart rate.
Further Information
Get more info on 'Potassium Channel'.
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