Lowering extracellular K⁺ below 1 mM leads to calcium transients in astrocytes in the hippocampus (Dallwig et al., 2000, Cell Calcium 28, 247–259) as well as in the brainstem. It was hypothesized, that inwardly rectifying K⁺ channels (Kir) are involved in this calcium signal by mediating Ca²⁺ influx in low K⁺ enviroment. In the respiratory network astrocytes predominantly express the weakly inwardly rectifying K⁺ channel Kir4.1 (KCNJ10). Astrocytes lacking the Kir 4.1 channel show a depolarized resting membrane potential and a virtual lack of Ba²⁺ sensitive inward currents. To investigate, if the Kir4.1 channel is involved in low K⁺ induced calcium transients in VRG astrocytes, we loaded wild type and Kir4.1-/- mice acute brainstem slices with the membrane permeable fluorescent Ca²⁺ indicator Oregon Green. The number of cells, which showed calcium oscillations in the response to 0.2 mM potassium was significant reduced in Kir4.1-/- mice (7.5 ± 2.4 % ; mean ± SEM) as compared to controls (64.2 ± 11.6 %; P<0.001). Additionally, the duration of low K⁺ induced calcium oscillations in cells from Kir4.1-/- mice was also significantly reduced (76.6 ± 11.5 s; n=24) compared to controls (135.0 ± 10.8 s; n=50; P<0.001). Taken together, these data suggest, that the Kir4.1 channel is involved in the low K⁺ induced calcium oscillations in astrocytes. Supported by the DFG (Ne 767/3–1,3, De 231/19–1, Hu 797/3–1).