0xc9941dee…cc7dsent to0x81c094f7…aa23·#25,276,107·view on Etherscan
# The role of adsorbed water in the loop of Henle: osmosis and electricity
It is well established that water at hydrophilic surfaces forms a 2-3 atomic layers thick adsorbed phase. This adsorbate likely tends to be in what Gerald Pollack named "the fourth phase", ice-like but where the hydrogen atoms between the atomic honeycomb layers have been expelled, thus one in two H2O is ionized and the phase is (H3O2-)n (and the layers are shifted half an oxygen relative to one another). The expelled hydrogen ions are free to diffuse away, and a low pH region of pH 5.5 that extends outwards up to 1 cm is empirically known to form. When there is asymmetry in the thickness of adsorbate on either side of an osmotic membrane (from salt impairing adsorbate forming, or the effect from pressure as the adsorbate is denser than water), the hydrogen ions will tend to distribute themselves such that there is net transfer from the side with thicker membrane to the side with thinner membrane. This transfer leads to a net negative charge on the side with thicker adsorbate and a net positve on the side with thinner adsorbate - an electric field. This electric field drives transfer of negatively charged particles, trivially hydroxide ions from within the adsorbate, or, under the right conditions, electrons which can be released from hydroxide in the oxygen evolution reaction 4 OH- --> 2 H2O + O2 + 4 e- (although this requires external O2 at the side of the membrane water moves to, the endosmotic side). The adsorbate itself covering the membrane also serves as a barrier, reducing ability for anything else to transfer across the membrane (even if membrane itself would allow it). Traditional osmosis is most likely the transfer of OH- along the electric field, and the osmotic membranes themselves can have water adsorbed within it similar to a dishcloth providing a convientient path for the OH- transfer, and the electron-based osmosis ("redox osmosis") is something that can be easily built on top of this rudimentary machinery of osmosis, something exploited by the cell and biology as a whole (including electric circuits of proteins where K+ substituted the H+ externally, and all H+ is moved onto ATP within the protein where the charge is in 1:1 proportion with the K+ outside, K+ and PO4-3 being the primary intracellular ions for this reason). Within the kidney, traditional osmosis does the bulk of water reabsorbtion, while redox osmosis powers epithelium at thin ascending limb by providing electricity across it to drive membrane proteins (the chloride channels, ClC-Ka) for pumping salt out into the medulla to improve the osmotic gradient. Aquaporins likely support both traditional and redox-based osmosis, thus in the thin descending limb some O2 is also generated, which is then exploited at the thin ascending limb to provide electricity (and the water necessary for that loop comes from the collecting duct) - and O2 loops around between the loop of Henle and the vasa recta to drive the epithelium at the thin ascending limb. Carbohydrates such as glucose can react with the OH- in the adsorbate and then the oxidation produces CO2 instead of O2, which "short circuits" the O2 loop and reduces electricity delivered to thin ascending limb, resulting in collapse of the salt pumping and failure to concentrate urine. For osmosis through aquaporins, they are typically viewed as impermeable to protons, which they likely are at H+ concentrations such as pH 4 to pH 7, but locally the adsorbate is pOH -1.4, the protons released would tend to also diffuse into the aquaporin water channel which is continuous with the adsorbate thus the "pressure" for pushing protons across is a completely different magnitude than what is used in the experiments, and the same goes for OH- wanting to move through the water channel (where the protonated arginine at the center neatly binds a hydroxide ion).
The ClC-Ka protein moves both Cl-, H+ and e-. Likely, the Cl- and H+ salt-bond and the HCl hydrogen bonds to the thyrosine OH group. Electrons move by reducing the H+, and the interior is hydronium rich due to being adjacent to the adsorbate on either side of the plasma membrane (although extending out through it, to contact bulk water so Cl- can access it - contrary to the aquaporin). The redox osmosis "powers" this chloride pump. The protons pushed into the channel attract Cl- and they meet at the center. The e- then breaks the salt-bond at the center (reduced H+, H, does not ion bond...), moving either conjugate ion (H+ and Cl-) to either side. The H+ thus forms a local electric field that favours Cl- transport within the channel even if the larger external electric field is in the opposite direction (and it is what drives the osmosis). Historically, scientists have struggled with the lack of an active mechanism for the salt transfer in the thin ascending limb, and leaned on the passive explanation as the best they could think of. With this redox osmosis, there is then besides the passive concentration gradient mechanism also an active mechanism. The way the redox osmosis powers the pump (pump, i.e., a channel with active mechnism) is by providing two concentration gradients, H+ in one direction and Cl- in the other. The e- is necessary to sustain the movement of H+ (otherwise electrostatic charge imbalance and it stops) and O2 is necessary at the side the Cl- moves from for the H+ and e- transfer to be sustained, it makes the transfer "downhill" as H+ and e- want to end up reacting with O2 to form water, 4 H+ + 4 e- + O2 --> 2 H2O.