The many different potassium channels are constructed from a large number of subunits. They exist in varied compartments in the neuron. They are, also, different in the thousand different kinds of neurons in the brain (see post How Many Different Kinds of Neurons Are There). These potassium channels provide many varied functions and are found in multiple different compartments in proximal and distal dendrites and axons. Numerous types are specific to pre synaptic terminal regions, the cell bodies and at the nodes of Ranvier. With so many different types of neurons, it is only a little surprising that there would be a fantastic complexity in brain potassium channels

The neuron is unusual in that it uses two thirds of the genome to make a wide variety of proteins. It is, also, unusual in that one cell can be a yard long. The neuron's complexity is based on many different unusual cellular compartments and the use of proteins to provide the unique constantly changing structures for neuroplasticity. Large families of proteins in the neuron include channel molecules in the membrane that allow control of the flux of different ions including sodium, potassium and calcium. These channel proteins are used as receptors for signals from other cells (inotropic receptors) as well as signaling inside the cell. Potassium channels are the third largest group of proteins used for signaling in cells. (GPCR and kinases are the other two).

Almost A Hundred Different Potassium Channels

It is widely known that there are many different ionic receptors in synapses, such as sodium, calcium and inotropic glutamate receptors. But, it is not understood that there are, also, many unique potassium channels in each of the regions that are critical for neuronal transmission.

Eighty genes code for the basic channel subunits, called α units, with many additional proteins and cofactors forming a large potassium channel (KCh) complex. Various complexes with different subunits form unique types of channels throughout the brain. The exceptionally large number of different complex types is based on construction using either 2 or 4 different types of α units, along with multiple additional subunits.

Previous posts have described electrical phenomenon in and around neurons. They noted that the widespread conception of multiple action potentials being mathematically computed at the synapse is a simplification. Simple computation is upended by the vast complexity of different kinds of spikes, spatial and time factors, as well as many other synapse variables (see post The Limits of Current Neuroscience). In fact, there are a wide variety of local electrical gradients in neurons and along axons that have impact. The varied potassium channels have differing vital roles in these complex electrical events inside the neuron, along the axon and in between cells. The local potassium channel complexes respond to local environments and various other stimuli. Recently, several potassium channels have been shown to pick up both chemical and electrical signals serving as a coordinator of these

Potassium channels open and close allowing ions to move rapidly down a chemical gradient. They are specific to potassium and don't allow sodium, calcium, magnesium or any other ion. They can produce the resting electrical potential for a cell and can reset the potential after an electrical event. The shape of the axon's action potential is determined by the rate of the potassium flow after the sodium flow. In the heart, they keep the proper rhythm and when the general level of potassium is high or low, deadly heart rhythms can occur. They, also, maintain the tone of blood vessels and regulate secretion of insulin and other hormones.

One overly simplified view of the types of channels includes at least 6 dendrite types, 2 axon and terminal types, 4 dendrite and soma types, 9 intracellular and 16 unknown. Each type has many variations.

A more comprehensive classification is available online as a resource ((https://www.ipmc.cnrs.fr/$duprat/ipmc/nomenclature). This site describes 15 superfamilies with more than 90 subtypes. The families are called KCNA, KCNB, KCNAB, KCNC, KCND, KCNE, KCNF, KCNG, KCNH, KCNJ, KCNK, KCNM, KCNN, KCNQ, and KCNS.

Subunits and Cofactors of Different Channels
From AlexanderPico

From AlexanderPico

The primary subunits are called α units, which are proteins that cross the membrane multiple times (many cross six times, some four, two and one). They form a central pore that allows potassium to flow through or stops it from flowing. There are many other regions on the protein to provide many varied functions. The 80 genes manufacture 4 major types and many subtypes.

Four classes include:

Channels triggered by calcium or other signals. These are called Kir and use G proteins and ATP in cascades (fifteen types).

Channels that pass positive charge into the cell. These are called KCa and are activated by calcium and sodium (eight types).

Channels that are always open or "leak" to provide a basal negative membrane potential. These are called K2P and are triggered by oxygen tension, pH, mechanical stretch, and G-proteins (fifteen types).

Channels that are voltage gated responding to specific electrical gradients. These are called Kv (41 types).

Selectivity Filters

PD 1K4CWhen potassium ions enter the channel they are in a complex surrounded by water molecules. The channel has a mechanism, called the selectivity filter, to remove the shell of water from the ion as it enters the P loop of the proteins that cross the membrane. All of the different types of channels have basically the same five amino acid sequences in the selectivity filter.

The unique structure of this P loop has special carbonyl oxygen molecules facing the center of the channel with a charge of negative electricity. The position of the multiple oxygen in this structure is similar to oxygen in water that normally surrounds the ion. This positioning creates a path for the ion to shed its water. The electrical activity of the rest of the loop draws the extracellular water solution into the channel to perform the function of freeing the potassium ion. In fact, it is a vastly complex mechanism that responds to many different signals such as calcium, electrical voltage and others.

Two alpha subunits combine to form some channels and there are four in most. With many subunits available, one group can assemble together and others cannot. Typically four subunits combine and then many co factors collect to make a complex. These complexes have different abilities, functions, modulations and places of operation.

Manufacture of the subunits into a functioning channel is straightforward. But, it is not clear how different subunits and factors are present in particular regions of the membrane and how they are related to the pathways forming the specific types of membrane (see post on Amazing Complexity of Cellular Membranes).

After creation of the protein subunits by messenger RNA, it is not at all clear how they can be positioned all along the very large axon membrane. It is not understood why some are produced and not utilized at particular sites within the neuron and what directs this decision. In the neuron, the axon membrane can extend for a yard. Somehow, all along the axon specific channels are placed in very discrete locations and amounts.

The reason little is known about the vast array of different potassium subunits is that they are difficult to study in the human brain. The way proteins are studied relies upon labeling of subunits and following them in their travels. Tagged subunits cannot be followed in the human brain as in animal models. But, recent data has been supplied using antibodies for particular subunits.