Potassium channels function to conduct potassium ions down their electrochemical gradient, doing so both rapidly (up to the diffusion rate of K+ ions in bulk water) and selectively (excluding, most notably, sodium despite the sub-angstrom difference in ionic radius). Biologically, these channels act to set or reset the resting potential in many cells. In excitable cells, such as neurons, the delayed counterflow of potassium ions shapes the action potential.
- Calcium-activated potassium channel – open in response to the presence of calcium ions or other signalling molecules.
- Inwardly rectifying potassium channel – passes current (positive charge) more easily in the inward direction (into the cell).
- Tandem pore domain potassium channel – are constitutively open or possess high basal activation, such as the “resting potassium channels” or “leak channels” that set the negative membrane potential of neurons. (TASK-2)
- Voltage-gated potassium channel – are voltage-gated ion channels that open or close in response to changes in the transmembrane voltage.
Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a fourfold symmetric (C4) complex arranged around a central ion conducting pore (i.e., a homotetramer). Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C4 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.
Potassium ion channels remove the hydration shell from the ion when it enters the selectivity filter. The selectivity filter is formed by a five residue sequence, This sequence adopts a unique structure, having their electro-negative carbonyl oxygen atoms aligned toward the centre of the filter pore and form a square anti-prism. 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, providing an energetically favorable route for de-solvation of the ions. The selectivity filter opens towards the extracellular solution, exposing four carbonyl oxygens in a glycine residue. The next residue toward the extracellular side of the protein is the negatively charged 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 flux of ions through the potassium channel pore is regulated by two related processes, termed gating and inactivation. Gating is the opening or closing of the channel in response to stimuli, while inactivation is the rapid cessation of current from an open potassium channel and the suppression of the channel’s ability to resume conducting. While both processes serve to regulate channel conductance, each process may be mediated by a number of mechanisms.
Generally, gating is thought to be mediated by additional structural domains which sense stimuli and in turn open the channel pore. These domains include the RCK domains of BK channels, and voltage sensor domains of voltage gated K+ channels. These domains are thought to respond to the stimuli by physically opening the intracellular gate of the pore domain, thereby allowing potassium ions to traverse the membrane. Some channels have multiple regulatory domains or accessory proteins, which can act to modulate the response to stimulus.
N-type inactivation is typically the faster inactivation mechanism, and is termed the “ball and chain” model. N-type inactivation involves interaction of the N-terminus of the channel, or an associated protein, which interacts with the pore domain and occludes the ion conduction pathway like a “ball”. Alternatively, C-type inactivation is thought to occur within the selectivity filter itself, where structural changes within the filter render it non-conductive.