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

Domenico Vitarella, Harold K. Kimelberg, Michael Aschner

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalBrain Research
Volume732
Issue number1-2
DOIs
StatePublished - Sep 2 1996
Externally publishedYes

Fingerprint

Amiloride
Astrocytes
D-Aspartic Acid
Taurine
Permeability
Buffers
Ions
Furosemide
Electric Impedance
Cell Size
Glutamic Acid
Amino Acids

Keywords

  • astrocyte
  • methylmercury
  • potassium
  • sodium
  • taurine
  • volume regulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na+ uptake. / Vitarella, Domenico; Kimelberg, Harold K.; Aschner, Michael.

In: Brain Research, Vol. 732, No. 1-2, 02.09.1996, p. 169-178.

Research output: Contribution to journalArticle

@article{d15d0e4e814a4a7b91c1fab8d12b79ae,
title = "Inhibition of regulatory volume decrease in swollen rat primary astrocyte cultures by methylmercury is due to increased amiloride-sensitive Na+ uptake",
abstract = "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.",
keywords = "astrocyte, methylmercury, potassium, sodium, taurine, volume regulation",
author = "Domenico Vitarella and Kimelberg, {Harold K.} and Michael Aschner",
year = "1996",
month = "9",
day = "2",
doi = "10.1016/0006-8993(96)00518-5",
language = "English (US)",
volume = "732",
pages = "169--178",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1-2",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0030565508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030565508&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(96)00518-5

DO - 10.1016/0006-8993(96)00518-5

M3 - Article

C2 - 8891281

AN - SCOPUS:0030565508

VL - 732

SP - 169

EP - 178

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -