ASTROCYTE NA+ CHANNELS ARE REQUIRED FOR MAINTENANCE OF NA+ K+-ATPASE ACTIVITY/

Astrocytes in vitro and in situ have been shown to express voltage-act ivated ion channels previously thought to be restricted to excitable c ells, 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 cel ls, 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 astrocy te Na+ channels by TTX had multiple effects: (1) TTX reduced, in a dos e-dependent manner, Na+/K+-ATPase activity measured as unidirectional influx of Rb-86(+); (2) TTX depolarized astrocyte membrane potential a t a rate of approximately 1 mV/min; (3) TTX(100 mu M) reduced [Na+](i) ; and (4) prolonged exposure to micromolar TTX induced astrocyte death . All these effects of TTX could be mimicked by ouabain or strophanthi din, specific blockers of the Na+/K+-ATPase. The effects of TTX and ou abain (or strophanthidin) were not additive. These results suggest tha t TTX-blockable Na+ channels in glial cells serve functions that do no t require their participation in action potential electrogenesis; in p articular, we propose that glial Na+ channels constitute a ''return'' pathway for Na+/K+-ATPase function, which permits Na+ ions to enter th e cells to maintain [Na+](i) at concentrations necessary for activity of the Na+/K+-ATPase. Since astrocyte Na+/K+-ATPase is believed to par ticipate in [K+](o) homeostasis in the CNS, the coupling of Na+ flux t hrough 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.