Ion channel expression by white matter glia: I. Type 2 astrocytes and oligodendrocytes

Abstract

White matter is a compact structure consisting primarily of neuronal axons and glial cells. As in other parts of the nervous system, the function of glial cells in white matter is poorly understood. We have explored the electrophysiological properties of two types of glial cells found predominantly in white matter: type 2 astrocytes and oligodendrocytes. Whole-cells and single-channel patch-clamp techniques were used to study these cell types in postnatal rat optic nerve cultures prepared according to the procedures of Raff et al. (Nature, 303:390-396, 1983b). Type 2 astrocytes in culture exhibit a "neuronal" channel phenotype, expressing at least six distinct ion channel types. With whole-cell recording we observed three inward currents: a voltage-sensitive sodium current qualitatively similar to that found in neurons and both transient and sustained calcium currents. In addition, type 2 astrocytes had two components of outward current: a delayed potassium current which activated at 0 mV and an inactivating calcium-dependent potassium current which activated at -30 mV. Type 2 astrocytes in culture could be induced to fire single regenerative potentials in response to injections of depolarizing current. Single-channel recording demonstrated the presence of an outwardly rectifying chloride channel in both type 2 astrocytes and oligodendrocytes, but this channel could only be observed in excised patches. Oligodendrocytes expressed only one other current: an inwardly rectifying potassium current that is mediated by 30- and 120-pS channels. Because these channels preferentially conduct potassium from outside to inside the cell, and because they are open at the resting potential of the cell, they would be appropriate for removing potassium from the extracellular space; thus it is proposed that oligodendrocytes, besides myelinating axons, play an important role in potassium regulation in white matter. The conductances present in oligodendrocytes suggest a "modulated Boyle and Conway mechanism" of potassium accumulation.

Electrophysiological Changes That Accompany Reactive GliosisIn Vitro

“…This K IR current was identical in its kinetics and voltage dependence to those previously described for spinal cord astrocytes in vitro and in situ (Sontheimer et al, 1992;Ransom and Sontheimer, 1995). As we (Ransom and Sontheimer, 1995) and others (Barres et al, 1988;Tse et al, 1992;Newman, 1993) have described previously, K IR currents were highly sensitive to 100 M extracellular Cs ϩ (Fig. 6G).…”

Astrocytes and Epilepsy

“…[26][27][28][29][30][31] Comparative patch-clamp studies were carried out on astrocytes in hippocampal specimens with and without significant sclerosis removed in epilepsy surgery. In a study from our laboratory, primary cultures of astrocytes established from the hippocampus (dentate gyrus and Ammon's horn) and parahippocampus (entorhinal region) of sclerotic hippocampi displayed much larger tetrodotoxin (TTX)-sensitive Na ϩ currents with ϳ66-fold higher Naϩ channel density than in astrocytes from nonsclerotic hippocampi and comparison temporal neocortex of the same patient 32 (FIG.…”

Astrocytes from Human Hippocampal Epileptogenic Foci Exhibit Action Potential–Like Responses

“…However, overshooting responses mediated by Ca2+ channels have been reported in currentclamped cerebral astrocytes (22). AP-like responses were also reported in rat optic nerve type 2 astrocytes (undifferentiated progenitor cells) (20), which required large current injections, and membranes did not repolarize after a single response. During development in culture, spinal cord astrocytes expressed high levels of Na+ channels and were capable of an AP-like response to a current injection (34).…”