H. Sontheimer et al., ASTROCYTE NA+ CHANNELS ARE REQUIRED FOR MAINTENANCE OF NA+ K+-ATPASE ACTIVITY/, The Journal of neuroscience, 14(5), 1994, pp. 2464-2475
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.