AJP - Cell Physiology, Vol 263, Issue 6 C1282-C1288, Copyright © 1992 by American Physiological Society
Osmoregulation of Na(+)-inositol cotransporter activity and mRNA levels in brain glial cells
A. Paredes, M. McManus, H. M. Kwon and K. Strange
Department of Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
During plasma hypertonicity brain volume is regulated acutely by
electrolyte uptake and chronically by accumulation of organic solutes such
as inositol. Cultured rat C6 glioma cells, an astrocyte-like cell line,
show a similar pattern of volume control. Volume regulatory accumulation of
inositol requires external inositol, indicating that membrane transport
plays a central role in this process. The inositol uptake pathway is Na+
dependent and exhibits Michaelis-Menten kinetics. Chronic hypertonic
acclimation results in a twofold increase in the maximum velocity of the
transporter without changing the Km. Hypertonic stress also results in a
17-fold increase in transporter mRNA. Elevation of mRNA levels precedes
activation of the transporter by 4-6 h, suggesting that increased inositol
uptake is mediated by synthesis and membrane insertion of new transport
proteins. Reacclimation of hypertonic cells to isotonicity causes a rapid
reduction of transporter mRNA levels to control levels within 4 h. In
contrast, downregulation of transport activity does not begin until between
10 and 24 h after reexposure to isotonicity.
