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Journal of Neuroscience, Vol 14, 2464-2475, Copyright © 1994 by Society for Neuroscience
Astrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity
H Sontheimer, E Fernandez-Marques, N Ullrich, CA Pappas and SG Waxman
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510.
Astrocytes in vitro and in situ have been shown to express voltage-
activated ion channels previously thought to be restricted to excitable
cells, including voltage-activated Na+, Ca2+, and K+ channels. However,
unlike neurons, astrocytes do not generate action potentials, and the
functional role of voltage-activated channels in astrocytes has been an
enigma. In order to study the function of Na+ channels in glial cells, we
carried out ion flux measurements, patch-clamp recordings, and ratiometric
imaging of [Na+]i during blockade of Na+ channels on rat spinal cord
astrocytes cultured for 7-10 d. Acute blockade of astrocyte Na+ channels by
TTX had multiple effects: (1) TTX reduced, in a dose- dependent manner,
Na+/K(+)-ATPase activity measured as unidirectional influx of 86Rb+; (2)
TTX depolarized astrocyte membrane potential at a rate of approximately 1
mV/min; (3) TTX (100 microM) reduced [Na+]i; and (4) prolonged exposure to
micromolar TTX induced astrocyte death. All these effects of TTX could be
mimicked by ouabain or strophanthidin, specific blockers of the
Na+/K(+)-ATPase. The effects of TTX and ouabain (or strophanthidin) were
not additive. These results suggest that TTX-blockable Na+ channels in
glial cells serve functions that do not require their participation in
action potential electrogenesis; in particular, we propose that glial Na+
channels constitute a "return" pathway for Na+/K(+)-ATPase function, which
permits Na+ ions to enter the cells to maintain [Na+]i at concentrations
necessary for activity of the Na+/K(+)-ATPase. Since astrocyte
Na+/K(+)-ATPase is believed to participate in [K+]o homeostasis in the CNS,
the coupling of Na+ flux through voltage- activated Na+ channels to ATPase
activity may provide a feedback loop that participates in the regulation of
K+ ion levels in the extracellular space.
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