The Journal of Neurophysiology Vol. 78 No. 6 December 1997, pp. 3249-3258
Copyright ©1997 The American Physiological Society

Pharmacological Characterization of Na⁺ Influx via Voltage-Gated Na⁺ Channels in Spinal Cord Astrocytes

Christine R. Rose^{1, 2}, Bruce R. Ransom³, and Stephen G. Waxman^{1, 2}

¹ Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520; ² Neuroscience Research Center, Veterans Affairs Hospital, West Haven, Connecticut 06516; and ³ Department of Neurology, University of Washington School of Medicine, Seattle, Washington 98195-6465

Rose, Christine R., Bruce R. Ransom, and Stephan G. Waxman. Pharmacological characterization of Na⁺ influx via voltage-gated Na⁺ channels in spinal cord astrocytes. J. Neurophysiol. 78: 3249-3258, 1997. Spinal cord astrocytes display a high density of voltage-gated Na⁺ channels. 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 sodium-binding benzofuran isophthalate. Stellate and nonstellate 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 µM tetrodotoxin (TTX). Inhibition of Na⁺ channel inactivation by veratridine (100 µM) evoked a [Na⁺]_i increase of 47.1 mM in 44% of stellate and 9.7 mM in 64% of nonstellate 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 (-)scorpion toxin and usually were 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-N-methyl-D-aspartate 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.