Recovery from lactacidosis-induced glial cell swelling with the aid of exogenous anion channels.

Abstract:

:Hypotonic challenge induces transient swelling in glial cells, which is typically followed by a regulatory volume decrease (RVD). In contrast, lactic acidosis (lactacidosis) induces persistent cell swelling in astrocytes without an accompanying RVD. In the present study, we studied the mechanisms by which lactacidosis interferes with normal volume regulation in rat astrocytic glioma C6 cells. Following exposure of C6 cells to a hypotonic challenge, a current was detected that exhibited properties consistent with those of volume-sensitive outwardly rectifying (VSOR) anion channels. When exposed to in vitro conditions designed to simulate lactacidosis, C6 cells failed to respond to hypotonic stress with an RVD, and VSOR anion currents were not activated. When added to C6 cells, an anion channel-forming protein purified from Helicobacter pylori, VacA, was found to form anion-selective channels in the plasma membrane, and the activity of the VacA channel was not affected by lactacidosis (pH 6.2). Cells preincubated with VacA and then exposed to lactacidotic conditions underwent transient swelling followed by RVD. In contrast, application of a cation ionophore, gramicidin, failed to inhibit lactacidosis-induced persistent cell swelling. From these results, we conclude that inhibition of a volume-sensitive anion channel contributes to persistent swelling induced by lactacidosis in glial cells. Introduction of anion channel activity into glial cells might provide a novel approach for treating cerebral edema, which is associated with lactacidosis in cerebral ischemia or head injury.

journal_name

Glia

journal_title

Glia

authors

Nabekura T,Morishima S,Cover TL,Mori S,Kannan H,Komune S,Okada Y

doi

10.1002/glia.10190

subject

Has Abstract

pub_date

2003-02-01 00:00:00

pages

247-59

issue

3

eissn

0894-1491

issn

1098-1136

journal_volume

41

pub_type

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