The control by internal calcium of membrane permeability to sodium and potassium

Abstract

SUMMARY1. A study has been made of the relationship between the concentration of internal calcium and the permeability of human red cell membranes to sodium and potassium.2. Fresh red cells contain very little calcium, but after being depleted of ATP by ageing they took up calcium from Ringer solution. The entry was unaffected by external sodium and potassium but was markedly pH dependent. When supplied with energy, calcium-loaded cells actively extruded calcium by a saturable process which was also unaffected by the distribution of sodium and potassium across the membranes. The activity of the calcium pump was sufficient to maintain the low internal concentration found under physiological conditions.3. Raising internal calcium in metabolically poor cells caused a loss of cell potassium which was greater than the concomitant sodium gain. These changes were reversed when ATP was supplied. External calcium had no effect. The increase in permeability to sodium and potassium was enhanced by the simultaneous addition of fluoride, and, even more so, of iodoacetate. These inhibitors had no effect on membrane permeability unless calcium was also present. Inosine potentiated the action of fluoride and iodoacetate in causing potassium loss, by allowing more calcium to enter the cells.4. The results suggest that the permeability of human red cell membranes to sodium and potassium is regulated by internal calcium, which in turn is controlled by a calcium pump that utilizes ATP.

The influx of calcium ions into human erythrocytes during cold storage. The influences of extracellular pH, intracellular adenosine triphosphate and efflux of univalent cations

“…When erythrocytes were cold-stored in iso-osmotic sucrose or isoosmotic KCI, the rates at which the cells became depleted of ATP were similar ( (Long & Mouat, 1973), enough remained to function as substrate for the Ca2+-activated adenosine triphosphatase and to cause efflux of Ca2+ from Ca2+-loaded cells when these were subsequently incubated at 37°C. In this respect the results differ from those of Lew (1970Lew ( , 1971 and Romero & Whittam (1971), who worked at 37'C and found the ATP contents of the cells to be of prime importance. This apparent discrepancy is most simply explained in terms of temperature.…”

“…Lew (1970Lew ( , 1971 showed that Ca2+ influx at 37°C from a saline medium occurred only after the cells had become depleted of their ATP content. Romero & Whittam (1971) confirmed this and further demonstrated that for ATP-depleted erythrocytes, also incubated under similar conditions, Ca2+ influx was strongly pH-dependent; it did not occur at pH 7.0 or below, but was appreciable at higher pH values. Long & Mouat (1973), on the other hand, used fresh erythrocytes and worked at low temperature to minimize any interfering effects of cell metabolism.…”

“…Loss of ATP from erythrocytes during cold storage in iso-osmotic sucrose or KCI Since Lew (1970Lew ( , 1971 and Romero & Whittam (1971) both demonstrated that Ca2+ influx at 37°C was observed only with cells of low ATP content, measurements have been made of the ATP contents of erythrocytes after cold storage in iso-osmotic sucrose or KCI, containing 2.5mM-CaC12. The results are shown in Table 1.…”

“…If this should also prove to be the case in the cold-storage procedure of Long & Mouat (1973), then it might be possible to explain their observations in terms of the pH-dependence of Romero & Whittam (1971).…”

Injections of calcium ions into spinal motoneurones

“…But in addition to this principal action, Ca2+ may also cause some increase in JNa' since the resting potential in our experiments was often relatively little changed, or even became a little more positive (coupling artifacts probably exaggerated this effect). In this respect, the motoneurones may behave like red blood cells, in which a rise in free Ca2+ level increases first the K+ permeability and then the Na+ permeability (Whittam, 1968;Romero & Whittam, 1971).…”