Kir4.1 channels contribute to astrocyte CO/H-sensitivity and the drive to breathe.

Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO/H, however, it is not clear how these cells detect changes in CO/H. Considering Kir4.1/5.1 channels are CO/H-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO/H sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to high levels of CO, which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO/H and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior.