Biological Membranes - A. N. Ogurtsov 2012

Electrogenesis of Biomembranes
Ion Channels
Non-regulated Potassium Channels

Cell/30.html">The Plasma Membrane of Cells contains numerous open potassium channels and very few channels for Na⁺, Ca²⁺, and Cl^- ions. As a result, the primary flux of ions across the plasma membrane is the outward flow of potassium ions from the Cytosol, which leads to a negative charge of the cytosol relative to the extracellular environment. The permeability of such potassium channels is independent of Membrane Potential or the presence of signaling molecules; therefore, these channels are referred to as nongated channels.

Nongated potassium channels play a major role in establishing the resting membrane potential in animal cells.

However, in plant and fungal cells, the negative potential of the cytosol is maintained by The activity of P-Class proton pumps, which actively pump protons out of The Cell cytosol.

Selectivity filters of Ion Channels. Experimental studies on the molecular Structure of ion channels have demonstrated that the principles of Structural and functional Organization of ion channel Proteins are conserved across all organisms. Bacterial membrane ion channels were the first to be studied in detail, serving as model systems for molecular biologists and biophysicists.

Bacterial potassium channels, much like other potassium channels, are composed of four identical protein subunits arranged symmetrically around a central pore.

Each subunit contains two transmembrane a-helices (S5 and S6) and a short P-segment (pore domain) (Figure 91).

Figure 91 - Schematic diagram of one of the four subunits of the bacterial potassium channel from Streptomyces lividans

In the tetrameric potassium channel, eight transmembrane a-helices form a Spatial Structure resembling an inverted cone (a "wigwam"), the interior of which creates a cavity known as the vestibule. This vestibule serves as the entrance to the channel and is located in the central region of the tetrameric protein (Figure 92).

Four protein loops, which are part of the subunit P-segments, form a selectivity filter (pore, narrow constriction) for K⁺ ions just above the exoplasmic surface of the membrane.

The selectivity of the filter for potassium ions is explained by the fact that a hydrated potassium ion, leaving the cytosol and binding non-covalently to the carbonyl oxygens of Glycine residues in the P-loop, leaves its attached Water molecules behind in the channel entrance cavity. The energetic penalty associated with ion dehydration is thus offset by the energy gained from forming non-covalent bonds between the potassium ion and the glycine carbonyl oxygens (Figure 93(a)).

Figure 92 - Schematic diagram of the nongated bacterial potassium channel from Streptomyces lividans: a - side cross-section, b - frontal view

For sodium ions, forming bonds with these same oxygens is much less favorable because the topology of the potassium channel is specifically tailored to the dimensions of a potassium ion rather than a sodium ion (Figure 93(b)).

Figure 93 - Schemes of ion coordination by water molecules and glycine carbonyl oxygens in the potassium channel: a - for K⁺, b - for Na⁺

The ionic radii of oxygen, potassium, and sodium are 1.4, 1.33, and 0.95 Å, respectively (1 nm = 10 Å).

The ring of oxygen atoms is positioned such that the K⁺-O distance (1.4 + 1.33 = 2.73 Å) is optimal for the interaction between oxygens and potassium. For sodium, the Na⁺-O bond is shorter (0.95 + 1.4 = 2.35 Å).

Consequently, the energy penalty of dehydration for sodium exceeds the energetic gain from binding an Na⁺ ion within the channel, preventing the spontaneous diffusion of Na⁺ ions through the potassium channel (Figure 94(b)).

Figure 94 - Energetics of K⁺ channel selectivity: a - for K⁺, b - for Na⁺

X-ray crystallographic analysis of potassium channels has revealed that they retain potassium ions within the selectivity filter even when equipped with protein gates. Presumably, the presence of potassium ions stabilizes the channel structure, and in their absence, the tetramer would dissociate.

There are four potassium ion binding sites within the selectivity filter (Figure 95).

It is hypothesized that two potassium ions can simultaneously occupy positions 1 and 3 (Figure 96(a)), or positions 2 and 4 (Figure 96(b)), with each ion coordinated by eight carbonyl oxygens.

Figure 95 - Cross-section of a K⁺ channel selective filter. The numbers indicate the non-covalent K binding sites within the channel

The presence of two ion-binding sites in the channel: (1 and 3) or (2 and 4) is essential to ensure the rapid release of ions from the channel into the extracellular space.

Figure 96 - Position of potassium ions within the channel

The potassium channel is permeable in both directions to potassium ions. However, a higher concentration of potassium ions in the Cytoplasm promotes more frequent translocation of potassium ions from the solution into position 4 of the channel.

Electrostatic repulsion between cations triggers the transition of an ion from position 3 to position 2, while the ion from position 1 exits into the exoplasm and is immediately hydrated (Figure 96(6)).

Sodium channels share a similar architecture. They allow sodium ions to pass through, whereas larger potassium and Calcium Ions simply cannot squeeze into the channel.