Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na⁺ uptake

Primary astrocyte cultures from neonatal rats were swollen by exposure to hypotonic buffer with and without 10 μM methylmercury (MeHg). We investigated the effects of MeHg on K⁺ (using ⁸⁶Rb), taurine, D-aspartate (a non metabolizable analogue of glutamate) and Na⁺ fluxes during regulatory volume decrease (RVD), with an electrical impedance method for determination of cell volume, coupled with on-line measurements of efflux of radioactive ions and amino acids. Addition of 10 μM MeHg completely inhibited RVD in swollen astrocytes, increased the uptake of ²²Na⁺, increased ⁸⁶Rb release, and decreased ³H-taurine release. There was no effect on the rate of release of ³H-D-aspartate from swollen astrocytes. 0.5 mM amiloride completely inhibited MeHg-induced increased Na⁺ influx during RVD, while 1 mM furosemide had no effect. When Na⁺ in the hypotonic buffer was replaced with N-methyl-D-glucamine (NMDG), RVD in the presence of MeHg was indistinguishable from controls. These results indicate that MeHg increases cellular permeability to ions such as Na⁺ and K⁺, and that an increase in Na⁺ permeability via Na⁺/H⁺ exchange, offsetting K⁺ loss, is the primary mechanism in its inhibition of RVD in swollen astrocytes.