Regulation of the sodium permeability of the luminal border of toad bladder by intracellular sodium and calcium: role of sodium-calcium exchange in the basolateral membrane.

Abstract

Sodium movement across the luminal membrane of the toad bladder is the rate-limiting step for active transepitheliaI transport. Recent studies suggest that changes in intracellular sodium regulate the Na permeability of the luminal border, either directly or indirectly via increases in cell calcium induced by the high intracellular sodium. To test these proposals, we measured Na movement across the luminal membrane (the Na influx) and found that it is reduced when intracellular Na is increased by ouabain or by removal of external potassium. Removal of serosal sodium also reduced the influx, suggesting that the Na gradient across the serosal border rather than the cell Na concentration is the critical factor. Because in tissues such as muscle and nerve a steep transmembrane sodium gradient is necessary to maintain low cytosolic calcium, it is possible that a reduction in the sodium gradient in the toad bladder reduces luminal permeability by increasing the cell calcium activity. We found that the inhibition of the influx by ouabain or low serosal Na was prevented, in part, by removal of serosal calcium. To test for the existence of a sodium-calcium exchanger, we studied calcium transport in isolated basolateral membrane vesicles and found that calcium uptake was proportional to the outward directed sodium gradient. Uptake was not the result of a sodium diffusion potential. Calcium efflux from preloaded vesicles was accelerated by an inward directed sodium gradient. Preliminary kinetic analysis showed that the sodium gradient changes the Vm, x but not the Km of calcium transport. These results suggest that the effect of intracellular sodium on the luminal sodium.permeability is due to changes in intracellular calcium.

Calcium transport in canine renal basolateral membrane vesicles. Effects of parathyroid hormone.

“…6). Calcium taken up by the BLMV on the basis of the inwardly directed Ca2' chemical potential was, in part, effluxed uphill in the presence of a Na' gradient (26). Relationship of the Na+/Ca2+ exchange activity to external Na' concentration.…”

Nedd4–2 isoforms differentially associate with ENaC and regulate its activity

“…10). cAMP, ATP, and norepinephrine have been reported to induce a similar Cl Ϫ secretion profile in M-1 cells, and at least the ATP effect is mediated by an increase in [Ca 2ϩ ] i (9,10,32,51 Earlier studies in other models of the collecting duct demonstrated that elevation of [Ca 2ϩ ] i reduces ENaC activity, although at least one prior study was unable to confirm this effect in M-1 cells (7,26,34,40). The mechanism for the inhibitory effect on Na ϩ transport is unknown, but an attractive hypothesis is that elevated [Ca 2ϩ ] i targets the C2-containing form of Nedd4 -2 to the plasma membrane where it can interact with ENaC, leading to channel internalization.…”

Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.

“…Second, a role for Gi in the action of PGE2 was examined using pertussis toxin. Finally, the possible role of increased cell cyclic AMP was examined using exogenous 8 Frindt and Windhager suggested that calcium inhibits Na' entry through the apical amiloride-sensitive sodium channel (27). Their data argue against inhibition of JNa by a direct action of Ca"+ on the basolateral Na+/K+-ATPase because ionomycin-induced inhibition ofJNa was reversed by amphotencin.…”