TY - JOUR
T1 - Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na+ uptake
AU - Vitarella, Domenico
AU - Kimelberg, Harold K.
AU - Aschner, Michael
N1 - Funding Information:
This study was supported in part by PHS Grants NIEHS 07331 awarded to M.A., and NS 23750 and NS 30303 awarded to H.K.K., and R-819210. The authors would also like to thank E. Rutledge for his helpful discussion of the data.
PY - 1996/9/2
Y1 - 1996/9/2
N2 - 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.
AB - 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.
KW - astrocyte
KW - methylmercury
KW - potassium
KW - sodium
KW - taurine
KW - volume regulation
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U2 - 10.1016/0006-8993(96)00518-5
DO - 10.1016/0006-8993(96)00518-5
M3 - Article
C2 - 8891281
AN - SCOPUS:0030565508
SN - 0006-8993
VL - 732
SP - 169
EP - 178
JO - Brain research
JF - Brain research
IS - 1-2
ER -