The Journal of Neuroscience, September 15, 1998, 18(18):7127-7137
Involvement of Stretch-Activated Cl
Channels in
Ramification of Murine Microglia
Claudia
Eder,
Rolf
Klee, and
Uwe
Heinemann
Department of Neurophysiology, Institute of Physiology, Humboldt
University, D 10117 Berlin, Germany
A stretch-activated Cl
current
(ICl) was investigated in cultured
murine microglia using the whole-cell configuration of the patch-clamp
technique. After application of membrane stretch, a
Cl current appeared within seconds, and its
amplitude increased further within 3-8 min.
ICl underwent rundown, which was prevented by addition of 4 mM ATP to the intracellular perfusing
solution. The stretch-activated Cl current
exhibited outward rectification and did not show any voltage-dependent
gating. Lowering the concentration of extracellular Cl from 142 to 12 mM by equimolar
substitution of Cl with gluconate shifted the
reversal potential of ICl by 41.6 ± 1.8 mV in the depolarizing direction.
4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) and
4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS)
blocked ICl in a voltage- and time-dependent
manner. At a test potential of +40 mV, a half-maximal blockade at 16.1 µM DIDS and at 71.0 µM SITS was determined
for ICl. At a concentration of 200 µM, 5-nitro-2-(3-phenylpropylamino)benzoic acid or
flufenamic acid blocked ICl by 88% and
75%, respectively. Each of these four Cl channel
blockers reversibly inhibited the ramification process of microglia,
whereas blockers of voltage-gated Na+ and
K+ channels did not affect the transformation of
microglia from their ameboid into the ramified phenotype. It is
suggested that in microglia functional stretch-activated
Cl channels are required for the induction of
ramification but not for maintaining the ramified shape.
Key words:
brain macrophages; ramification; stretch-activated
Cl current; SITS; DIDS; NPPB; flufenamic acid
Copyright © 1998 Society for Neuroscience 0270-6474/98/18187127-11$05.00/0
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