Genetic ablation of smooth muscle K IR 2.1 is inconsequential to the function of mouse cerebral arteries.

Cerebral blood flow is a finely tuned process dependent on coordinated changes in arterial tone. These changes are strongly tied to smooth muscle membrane potential and inwardly rectifying K + (K IR ) channels are thought to be a key determinant. To elucidate the role of K IR 2.1 in cerebral arterial tone development, this study examined the electrical and functional properties of cells, vessels and living tissue from tamoxifen-induced smooth muscle cell (SMC)-specific K IR 2.1 knockout mice. Patch-clamp electrophysiology revealed a robust Ba 2+ -sensitive inwardly rectifying K + current in cerebral arterial myocytes irrespective of K IR 2.1 knockout. Immunolabeling clarified that K IR 2.1 expression was low in SMCs while K IR 2.2 labeling was remarkably abundant at the membrane. In alignment with these observations, pressure myography revealed that the myogenic response and K + -induced dilation were intact in cerebral arteries post knockout. At the whole organ level, this translated to a maintenance of brain perfusion in SMC K IR 2.1 -/- mice, as assessed with arterial spin-labeling MRI. We confirmed these findings in superior epigastric arteries and implicated K IR 2.2 as more functionally relevant in SMCs. Together, these results suggest that subunits other than K IR 2.1 play a significant role in setting native current in SMCs and driving arterial tone.