Potassium channel

Of potassium channel ( Sheet Potassium Channel ) indicates an ion channel that allows the passage of potassium ions in a specific manner. The transport of potassium ions through the potassium channel occurs passively by diffusion. Its direction is determined by the electrochemical driving force to potassium ions.

Mechanisms of activation of different potassium channels

Voltage -activated potassium channels

Voltage -activated potassium channels ( TCDB ​​: 1.A.1.2 ) open with changes in membrane potential and support eg repolarization during the action potential of a neuron. The activation of this potassium channel type is performed by membrane depolarization at the same potential as the threshold of the sodium channel. However, the opening of the potassium channel of this type occurs much more slowly and lasts longer than that of the sodium channel.

Another voltage- activated potassium channel opens and closes during the depolarization extremely rapidly ( 10-4 to 10-5 s ) caused so short a repolarizing potassium efflux (A- current, engl. A -current, IA) and thus enables a rapid "firing " of nerve cells.

It differs outwardly and inwardly rectifying potassium channels ( outward rectifier / inward rectifier ).

Calcium -activated potassium channels

( TCDB ​​: 1.A.1.3 ) you open with a sharp increase in intracellular calcium ion concentration and repolarize or hyperpolarize the cell membrane thereby.

G-protein activated potassium channels

This is to potassium channels, which are directly regulated by G- proteins or indirectly through second messengers. After activation of the G protein- coupled receptor (GPCR ) with the ligand (e.g., acetylcholine, in the case of the muscarinic acetylcholine receptor ) is exchanged in the G.alpha - subunit of the G protein by GTP GDP. In the thus activated protein now solves the α - unit from the rest, which Gβγ can bind to the potassium channel and opens it. This will remain open until the bound GTP is hydrolyzed to GDP and G.alpha back to the subunits regroup. An important role of these channels in the regulation of heart rate by the parasympathetic part of the autonomic nervous system and at inhibitory synapses in the central nervous system.

Mechanically activated potassium channels

They are opened by train or on the membrane. That is how, for example, potassium channels at the stereocilia tip links, so the sensory hair cells in the inner ear.

ATP-sensitive potassium channels

They open when the cellular ATP content decreases, and for example, in the insulin- producing beta cells of the pancreas as well as in neurons of the hypothalamus contain.

ATP-sensitive potassium channels ( TCDB ​​: 1.A.2 ) are an important component of the blood glucose sensor system. They consist of an outer ring, composed of four identical regulatory subunits, termed SUR1 and an inner ring, composed of four identical, smaller sub-units, referred to as Kir6.2 surrounding the central pore. The object of the ATP - sensiviten potassium channels in the beta cell of the pancreas is to link the nutritional metabolism of the beta - cell membrane with their electrical activity. If the blood sugar levels low, little ATP can be formed by the cell, the ATP-sensitive potassium channel is open, on the membrane of the beta cell to a resting membrane potential is formed. Increases in blood sugar levels, more glucose passes through the dependent not of insulin glucose transporter 2 in the beta cell, there may be more energy-rich ATP are formed. ATP binds to the regulatory subunit of the ATP-sensitive potassium channel, the potassium channel is closed. This leads to an increase in the intracellular potassium concentration, membrane potential declines, it comes to depolarization. By the depolarization voltage-dependent calcium channels are opened, it comes to calcium influx into the cell. The increased intracellular calcium concentration is the signal for insulin - containing vesicles to fuse with the cell membrane and thus to secrete insulin. The increase in insulin then leads to the drop in blood sugar.

ATP-sensitive potassium channels are blocked by drugs selected from the group of the sulfonylureas. Activating mutations in the ABCC8 gene encoding the regulatory subunits ( SUR1 ) of the ATP-sensitive potassium channel, are responsible for approximately 12% of cases of congenital diabetes mellitus of the newborn ( neonatal diabetes mellitus). Activating mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP - sensitive potassium channel, underlie approximately 35-58 % of cases of neonatal diabetes. Neonatal diabetes mellitus can be successfully treated with sulfonylureas. Inactivating mutations in the gene ABCC8 lead something on early childhood hypoglycemia ( Familial hyperinsulinemic hypoglycemia).

The potassium channel KIR4.1 found on glial cells in the central nervous system, especially in astrocytes, oligodendrocytes and Bergmann glial cells. The main task seems to be a spatial buffering of Kaliumgradienten to maintain the axonal impulse conduction. Knock -out mice lacking Kir4.1 showed a strong hypomyelination and axonal changes. In a subset of patients with multiple sclerosis IgG autoantibodies were found against the potassium channel. Mutations in the gene encoding KIR4.1 - KCNJ10 are associated with the EAST or sesame syndrome, which is associated with epilepsy, ataxia, and deafness renal tubulopathy.

Selectivity

Potassium channels form a pore in the membrane. On the extracellular side of the pore is called the selectivity filter. This pore is formed from the polypeptide backbone, with the carbonyl oxygen atoms of the peptide bonds are aligned so that they can "take over" the role of oxygen in the water molecules of the hydration shell of the potassium ion. This results in energetically stabilized positions of the potassium ion in the selectivity filter (more specifically, 4 ), whereby a dehydration and thus passage of the potassium ion is facilitated through the pore. Inside the pore, there is a pocket with water molecules, where the potassium ions are hydrated immediately. Sodium ions, for example, do not pass through the filter selectivity, even though they are smaller than potassium ions. The reason is that the carbonyl oxygen atoms are too far away for them and they therefore can not replace the oxygen atoms of the water (in this case no energy stabilization).

Inhibition of the potassium channel

Like other channels can also be specifically block potassium channels by molecules or peptides. Depending on the type of potassium channel are to various substances in the situation. For example, targeted calcium-dependent potassium channels can be blocked without affecting other channels are affected. Therefore, not every inhibitor has the same effect in the body, since the different channel types differ in the occurrence and function.

Often the inhibitor acts directly on the pore of the channel, by closing this (for example, the tetraethylammonium cation ), either from the outside or the inside of the channel. Many natural plant and animal venoms contain proteins that inhibit potassium channels. For example, over 40 peptides from scorpion toxins known to have an inhibitory effect on potassium channels. But insecticides such as apamin of the bee are specific for calcium-dependent potassium channels.