Objective: 

Na⁺ channel activity in cultured renal (A6) epithelium from Xenopus laevis is regulated by the solution osmolarity. In the present study we examined which pathway downstream of phospholipase A2 (PLA2) is involved.

Methods: 

A6 cells were grown on permeable supports and mounted into a water-jacketed (28°C) Ussing chamber. Transepithelial electrical measurements were made under open circuit conditions. The transepithelial conductance (Gt) was determined by pulsed current injections (DI =1mA) and I_sc was calculated.

Results: 

A hypo-osmotic shock (from 260 to 160 mosm/kg H₂O) was induced after an equilibration period of 30 minutes by decreasing the NaCl concentration of the mucosal and serosal solutions. After 40 minutes exposure to hypotonicity the I_sc increased from 1.6±0.3 mA/cm² to 9.3±2.2 mA/cm² (n=8). In the presence of the PLA2 blocker quinacrine (100 mmol/l) I_sc only increased from 1.9±0.4 mA/cm² to 2.2±0.6 mA/cm² (n=4). In contrast, the inhibitor of Ca²⁺-insensitive PLA2, bromoenol lactone (10 mmol/l), the COX-1 inhibitor resveratrol (10 mmol/l), and the COX-2 inhibitor celecoxib (20 mmol/l) did not inhibit the hypo-induced increase in I_sc. In the presence of the 5-lipoxygenase inhibitor nordihydroguaiaretic acid (20 mmol/l) I_sc increased from 2.4±0.3 mA/cm² to 6.5±1.3 mA/cm² (n=6).

Conclusion: 

The data suggest that the leukotriene pathway might contribute to the osmotic regulation of sodium channel activity in A6 cells. Supported by FWO-Vlaanderen to P.S.