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Zhou M, Kimelberg HK: Freshly isolated astrocytes from rat hippocampus show two distinct current patterns and different [K (+)](o) uptake capabilities. J Neurophysiol. 2000 Dec;84(6):2746-57. Whether astrocytes predominantly express ohmic K (+) channels in vivo, and how expression of different K (+) channels affects [K (+)](o) homeostasis in the CNS have been long-standing questions for how astrocytes function. In the present study, we have addressed some of these questions in glial fibrillary acidic protein [GFAP (+)], freshly isolated astrocytes (FIAs) from CA1 and CA3 regions of P7-15 rat hippocampus. As isolated, these astrocytes were uncoupled allowing a higher resolution of electrophysiological study. FIAs showed two distinct ion current profiles, with neither showing a purely linear I-V relationship. One population of astrocytes had a combined expression of outward potassium currents (I (Ka), I (Kd)) and inward sodium currents (I (Na)). We term these outwardly rectifying astrocytes (ORA). Another population of astrocytes is characterized by a relatively symmetric potassium current pattern, comprising outward I (Kdr), I (Ka), and abundant inward potassium currents (I (Kin)), and a larger membrane capacitance (C (m)) and more negative resting membrane potential (RMP) than ORAs. We term these variably rectifying astrocytes (VRA). The I (Kin) in 70% of the VRAs was essentially insensitive to Cs (+), while I (Kin) in the remaining 30% of VRAs was sensitive. The I (Ka) of VRAs was most sensitive to 4-aminopyridine (4-AP), while I (Kdr) of ORAs was more sensitive to tetraethylammonium (TEA). ORAs and VRAs occurred approximately equally in FIAs isolated from the CA1 region (52% ORAs versus 48% VRAs), but ORAs were enriched in FIAs isolated from the CA3 region (71% ORAs versus 29% VRAs), suggesting an anatomical segregation of these two types of astrocytes within the hippocampus. VRAs, but not ORAs, showed robust inward currents in response to an increase in extracellular K (+) from 5 to 10 mM. As VRAs showed a similar current pattern and other passive membrane properties (e.g., RMP, R (in)) to "passive astrocytes"in situ (i.e., these showing linear I-V curves), such passive astrocytes possibly represent VRAs influenced by extensive gap-junction coupling in situ. Thus, our data suggest that, at least in CA1 and CA3 regions from P7-15 rats, there are two classes of GFAP (+) astrocytes which possess different K (+) currents. Only VRAs seem suited to uptake of extracellular K (+) via I (Kin) channels at physiological membrane potentials and increases of [K (+)](o). ORAs show abundant outward potassium currents with more depolarized RMP. Thus VRAs and ORAs may cooperate in vivo for uptake and release of K (+), respectively. |
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