6. Osmo-, volume and pH regulation

Question 1

pump-leak model of osmo- and volume regulation

Answer 1

This is a homeostatic regulation of the cell volume which operates in isotonic medium. The tendency of inorganic ions to reach thermodynamic equilibrium results in a net influx of ions (Donnan effect) which is counterbalanced by the Na+/K+ -pump. which reduces the ion content of the cell by 1 ion in each duty cycle. The resulting osmotic equilibrium is characterized by 0 net flow of the ions and therefore zero net movement of water. Inhibition of the Na+/K+ -pump will result in accumulation of ions and concomitantly accumulation of water even in an isotonic solution which will result in cell swelling.

Question 2

RVD (Regulatory volume decrease)

Answer 2

This cell volume regulatory mechanism is induced by cell swelling in hypotonic medium and leads to the reduction of the cell volume and loss of water even if the hypotonic condition is maintained. Short-term RVD means the net loss of inorganic ions which is followed by the loss of water. Long-term RVD means the reduction of the cytosolic osmolality by reducing the concentration of metabolites (metabolic regulation) either via efflux through transporters (e.g. taurine transporter) or by favoring anabolic processes.

Question 3

RVI (Regulatory volume increase)

Answer 3

This cell volume regulatory mechanism is induced by cell shrinkage in hypertonic medium and leads to the increase in the cell volume by gaining water even if the hypertonic condition is maintained. Short-term RVI means the net accumulation of inorganic ions which will be followed by the gain of water. Long-term RVI means the increase of the cytosolic osmolality by increasing the concentration of metabolites (metabolic regulation) either via metabolite influx through transporters (e.g. taurine transporter) or by favoring catabolic processes (i.e. converting polymers to monomers).

Question 4

steady-state pH of the cytosol

Answer 4

At this pH the rate of base efflux (e.g. the Cl-/HCO3- antiport) from the cells equals to the rate of the acid efflux (e.g. by the Na+/H+ antiport), both classes of transporters work at the same speed and thus the cytosolic pH remains constant. At this pH the graph of the pH-dependence of the acid efflux rate intercepts the pH-dependence of the base efflux rate.

Question 5

Na+/H+ antiport

Answer 5

An electroneutral exchanger in the cytoplasm membrane that mediates the influx of Na+ and the efflux of H+ from the cytosol. The main function of the transporter is the regulation of the cytosolic pH, running at high speed at acidic cytosolic pH and removing excess H+ from the cytosol, whereas the transport rate is reduced at alkaline cytosolic pH. In addition, the transporter also participates in regulatory volume increase (RVI) via the accumulation of Na+ in the cytosol and increasing intracellular osmolality.

Question 6

Cl-/HCO3- antiport

Answer 6

An electroneutral exchanger in the cytoplasm membrane that mediates the influx of 1 Cl- into, and the efflux of 1 HCO3- from the cytosol during one duty cycle. The main function of the transporter is the regulation of cytosolic pH, running at highs speed at alkaline pH and removing excess base (HCO3-) from the cytosol, whereas the transport rate is reduced when the cytosolic pH decreases. In addition, the transporter also participates in regulatory volume increase via the accumulation of Cl- in the cytosol, and thereby increasing intracellular osmolality.