Pharmacological Characterization of Na+ Influx via Voltage-Gated Na+
Channels in Spinal Cord Astrocytes.
Christine R. Rose, Bruce R. Ransom, and Stephen G. Waxman.
Department of Neurology, Yale University School of Medicine, New Haven, CT
06520; Neuroscience Research Center, VA Hospital, West Haven, CT 06516; and
Department of Neurology, University of Washington School of Medicine, Seattle,
WA 98195-6465. I. Physiologisches Institut, Universitat des Saarlandes, D-
66421 Homburg/Saar, Germany..
APStracts 4:190N, 1997.
ABSTRACT
Spinal cord astrocytes display a high density of voltage-gated Na+ channels.
In order to study the contribution of Na+ influx via these channels to Na+
homeostasis in cultured spinal cord astrocytes, we measured intracellular Na+
concentration ([Na+]i) with the fluorescent dye SBFI (sodium-binding
benzofuran isophthalate). Stellate and non-stellate astrocytes, which display
Na+ currents with different properties, were differentiated. Baseline [Na+]i
was 8.5 mM in these cells, and was not altered by 100 æM tetrodotoxin (TTX).
Inhibition of Na+ channel inactivation by veratridine (100 æM) evoked a [Na+]i
increase of 47.1 mM in 44% of stellate, and 9.7 mM in 64% of non-stellate
astrocytes. About 30% of cells reacted to veratridine with a [Na+]i decrease
of 2 mM. Qualitatively similar [Na+]i changes were caused by aconitine. The
effects of veratridine were blocked by TTX, amplified by (à-)scorpion toxin,
and were usually readily reversible. Veratridine-induced [Na+]i increases were
reduced upon membrane depolarization with elevated extracellular [K+].
Recovery to baseline [Na+]i was unaltered during blocking of K+ channels with
4-aminopyridine. [Na+]i increases evoked by the ionotropic non-NMDA receptor
agonist kainate were not altered by TTX. Our results indicate that influx of
Na+ via voltage-gated Na+ channels is not a prerequisite for glial Na+,K+-
ATPase activity in spinal cord astrocytes at rest, nor does it seem to be
involved in [Na+]i increases evoked by kainate. During pharmacological
inhibition of Na+ channel inactivation, however, Na+ channels can serve as
prominent pathways of Na+ influx and mediate large perturbations in [Na+]i,
suggesting that Na+ channel inactivation plays an important functional role in
these cells.
Received 11 April 1997; accepted in final form 8 August 1997.
APS Manuscript Number J298-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 28 August 1997