Volume Regulation and pH Homeostasis

Another Monovalent Cation: H⁺

H⁺ transport allows for control of cellular pH

cytosol pH (7.0-7.2) is generally lower than extracellular environment (7.4)
electrophysical gradient overcomes concentration gradient, so there is a passive influx

organelles are maintained at far from neutral pH (mitochondria=8, lysosome=5)

transport of H⁺ is nearly always secondary active transport, usually coupled to Na⁺influx

Na⁺/H⁺ Antiporter

removes H⁺ to prevent acidification of cell (which would occur due to the voltage gradient)

activated when pH falls

activated prior to each cell division

Na⁺-HCO₃^-/HCl Antiporter

another method of removing H⁺ from acidified cell

not well understood

twice as effective as Na⁺/H⁺, since the equivalent of two protons are being pumped per cycle

HCO₃^- is functionally equivalent to OH^-
it is produced from CO₂ + OH^-- (carbonic anhydrase), and CO₂ freely diffuses across membranes
transporting OH^- in one direction (in) does the same thing as transporting H⁺ in the other (out)

Cl^-/HCO₃^- Antiporter

removes OH^- to acidify cytosol

activated when pH rises

very important in red blood cell to move CO₂ out of the cell

H⁺ ATPase

moves H⁺ directly (e.g., into stomach)

Anion Transport

membrane potential reduces Cl^- influx

3 Cl^- transporters

e.g. CFTR secretes Cl^- onto respiratory gut epithelium, while Na⁺ enters paracellularly
stimulated by PKA, acts as ATPase but not coupled to ATP hydrolysis

Cell Volume Homeostasis

membranes are permeable to water, and concentration on either side tends to equalize

the Donnan effect

cells have a fixed negative charge inside (proteins, etc.) that cannot diffuse across the membrane
free negative charges diffuse, but fixed charges cannot, so neg. ion diff. is matched by pos. ion diff.
water follows the concentration gradient (Na⁺/K⁺ antiporter pushes out ions to prevent cell lysis)

fast response regulatory volume increase (RVI) and decrease (RVD) allow Na⁺ or K⁺ to follow gradient

RVI: avoid shrinkage by allowing NaCl entry (Na⁺/K⁺/2Cl^- or Na⁺/H⁺ + Cl^-/HCO₃^-)
RVD: avoid lysis by allowing KCl exit (stretch-activated K⁺ and Cl^-channels)