DIFFERENT NA+ CURRENTS IN P0-DERIVED AND P7-DERIVED HIPPOCAMPAL ASTROCYTES INVITRO - EVIDENCE FOR A SWITCH IN NA+ CHANNEL EXPRESSION INVIVO

Hippocampal astrocytes, derived from postnatal day zero (P0) rats, appear to be pluripotential with respect to sodium current expression in vitro, and display Na+ currents with h(infinity) midpoints close to -65 up to 5 days in vitro (DIV), and Na+ currents with midpoints close to -85 mV at 6 DIV and thereafter, These astrocytes also exhibit a biphasic pattern of Na+ current density, which is expressed at moderate levels at early times in vitro and decreases throughout the first 5 DIV, prior to expressing a second peak for the duration of time in culture. These observations have been interpreted as suggesting that astrocytes in these cultures display a 'switch' in Na+ channel biosynthesis, so that they express different types of Na+ current (with different h(infinity) curves) at early and later times in culture. To test the hypothesis that a similar switch in Na+ channel expression occurs in vivo, we have used patch-clamp methods to study Na+ current expression in astrocytes derived from rat hippocampus at various stages of postnatal development, P0, P4, P5 and P7. We observed a biphasic distribution of Na+ current density, which was highest in P0- and P7-derived astrocytes (18 pA/pF and 10.3 pA/pF, respectively); astrocytes derived at P4 and P5 did not express sodium currents. While P0-derived astrocytes show depolarized h(infinity) curves (midpoints close to -65 mV) at early times in culture, P7-derived astrocytes, studied at comparable times in vitro, display hyperpolarized h(infinity) curves (midpoints close to -85 mV). In addition, whereas the h(infinity) curves for P0-derived astrocytes show a discrete shift at about 5-6 DIV, the h(infinity) curves from P7-derived astrocytes do not change with increasing time in culture. Intermediate h(infinity) curve midpoints were not observed. Our data suggest that, with increasing age between P0 and P7 in vivo, there is initially a decline in Na+ channel biosynthesis, followed by a second wave of channel deployment with different steady-state inactivation properties. This may reflect the expression, in hippocampal astrocytes of two types of Na+ channels during different stages of development.