Astrocyte Na+ channels are required for maintenance of Na+/K(+)-ATPase activity

• Published in: The Journal of neuroscience Vol. 14; no. 5; pp. 2464 - 2475
• Main Authors: Sontheimer, H, Fernandez-Marques, E, Ullrich, N, Pappas, CA, Waxman, SG
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01-05-1994; Society for Neuroscience
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Astrocytes - enzymology; Astrocytes - physiology; Astrocytoma; Cell Line; Cells, Cultured; Electrophysiology - methods; Ganglia, Spinal - cytology; Ganglia, Spinal - physiology; Glioma; Membrane Potentials - drug effects; Membrane Potentials - physiology; Models, Biological; Ouabain - pharmacology; Rats; Rats, Sprague-Dawley; Rubidium - metabolism; Sodium - metabolism; Sodium Channels - drug effects; Sodium Channels - physiology; Sodium-Potassium-Exchanging ATPase - metabolism; Strophanthidin - pharmacology; Tetrodotoxin - pharmacology; Time Factors; Tumor Cells, Cultured
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.14-05-02464.1994

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.