Distinct electrophysiological alterations in dentate gyrus versus CA1 glial cells from epileptic humans with temporal lobe sclerosis.

Previous studies have characterized the electrophysiological properties of astrocytes in the CA1 region of hippocampi resected from patients with intractable temporal lobe epilepsy (TLE). However, the properties of hilar astrocytes from such patients have not been studied although astrocytes display regional heterogeneity and a non-uniform response to injury. Thus, we performed patch-clamp recordings of putative astrocytes in hilar and CA1 regions of surgically removed epileptic hippocampi with and without sclerosis (mesial TLE, MTLE patients, and paradoxical TLE, PTLE patients, respectively), and non-epileptic, non-sclerotic hippocampi (tumor patients). Our data show that the current profile of hilar astrocytes undergoes significant changes in MTLE but not in PTLE or tumor hippocampi. In particular, inwardly rectifying K(+) (K(IR)) and outwardly rectifying K(+) currents were reduced, inward Na(+) currents and membrane resistances were increased in putative astrocytes from MLTE cases compared to PTLE and tumor cases. Because the conductance of K(IR) channels in cell-attached patches (approximately 34pS) from MTLE tissue was not altered, a reduction in the number of K(IR) channels likely accounts for the decrease in whole-cell K(IR) conductance. Presumed astrocytes in the CA1 region from each patient group displayed intercellular coupling and a passive current profile; these characteristics were never observed in hilar glial cells. No apparent changes in the current profile of coupled CA1 glial cells could be detected between MTLE, PTLE and tumor tissues. Additionally, CA1 glial cells expressed a high density of 34pS K(IR) channels. These data suggest that K(+) buffering via K(IR) channels may be functionally compromised in hilar astrocytes of epileptic and sclerotic (MTLE) human hippocampi. By contrast, CA1 astrocytes retained their intercellular coupling and K(IR) channel expression necessary for K(+) buffering.