TY - JOUR
T1 - Methylmercury-induced inhibition of regulatory volume decrease in astrocytes
T2 - Characterization of osmoregulator efflux and its reversal by amiloride
AU - Aschner, Michael
AU - Vitarella, Domenico
AU - Allen, Jeffrey W.
AU - Conklin, Dawn R.
AU - Cowan, Kelly S.
N1 - Funding Information:
This study was supported in part by PHS grants NIEHS 07331 and USEPA 819210 awarded to M.A.
PY - 1998/11/16
Y1 - 1998/11/16
N2 - Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resting cell volume. RVD is associated with activation of conductive K+ and Cl- channels, allowing for the escape of KCl, as well as the release of osmoregulators, such as taurine and myoinositol. As we have previously shown [D. Vitarella, H.K. Kimelberg, M. Aschner, inhibition of RVD in swollen rat primary astrocyte cultures by methylmercury (MeHg) is due to increase amiloride-sensitive Na+ uptake, Brain Res. 732 (1996) 169-178.], MeHg, when added to hypotonic buffer inhibits RVD, primarily due to increased cellular permeability to Na+ via the Na+/H+ antiporter. The present study was, therefore, undertaken to assess the ability of cation-anion cotransport blockers to reverse the inhibitory effect of MeHg on RVD in swollen astrocytes, and to further characterize MeHg-induced changes in astrocytic osmoregulatory release processes. The studies demonstrate the following: (1) MeHg-induced inhibition of RVD is partially inhibited by the Na+/H+ antiporter blocker, amiloride, but not SITS (4-acetamido-4'- isothiocyanatostilbene-2,2'-disulfonic acid), DIDS (4,4'-diisothiocyano- 2,2'-stilbenedisulfonic acid), furosemide or bumetanide; (2) exposure of swollen astrocytes to MeHg is associated with specific effects on osmoregulatory release, leading to significant inhibition of taurine release and a significant increase in potassium and myoinositol release compared with release in hypotonic conditions.
AB - Swelling of neonatal rat primary astrocyte cultures by hypotonic media leads to regulatory volume decrease (RVD) and the resumption of resting cell volume. RVD is associated with activation of conductive K+ and Cl- channels, allowing for the escape of KCl, as well as the release of osmoregulators, such as taurine and myoinositol. As we have previously shown [D. Vitarella, H.K. Kimelberg, M. Aschner, inhibition of RVD in swollen rat primary astrocyte cultures by methylmercury (MeHg) is due to increase amiloride-sensitive Na+ uptake, Brain Res. 732 (1996) 169-178.], MeHg, when added to hypotonic buffer inhibits RVD, primarily due to increased cellular permeability to Na+ via the Na+/H+ antiporter. The present study was, therefore, undertaken to assess the ability of cation-anion cotransport blockers to reverse the inhibitory effect of MeHg on RVD in swollen astrocytes, and to further characterize MeHg-induced changes in astrocytic osmoregulatory release processes. The studies demonstrate the following: (1) MeHg-induced inhibition of RVD is partially inhibited by the Na+/H+ antiporter blocker, amiloride, but not SITS (4-acetamido-4'- isothiocyanatostilbene-2,2'-disulfonic acid), DIDS (4,4'-diisothiocyano- 2,2'-stilbenedisulfonic acid), furosemide or bumetanide; (2) exposure of swollen astrocytes to MeHg is associated with specific effects on osmoregulatory release, leading to significant inhibition of taurine release and a significant increase in potassium and myoinositol release compared with release in hypotonic conditions.
KW - Amiloride
KW - Astrocyte
KW - Cell swelling
KW - In vitro
KW - Methylmercury
KW - Myoinositol
KW - Rat
KW - Taurine
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U2 - 10.1016/S0006-8993(98)00629-5
DO - 10.1016/S0006-8993(98)00629-5
M3 - Article
C2 - 9804925
AN - SCOPUS:0032539065
SN - 0006-8993
VL - 811
SP - 133
EP - 142
JO - Brain research
JF - Brain research
IS - 1-2
ER -