Genetic ablation of smooth muscle KIR2.1 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 Ba2+-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.

Automated summary

Cerebral blood flow is finely regulated by changes in arterial tone, in which inwardly rectifying K+ channels play a key role. There is a strong Ba2+-sensitive inwardly rectifying K+ current in cerebral arterial myocytes, regardless of the presence of K(IR)2.1. K(IR)2.1 expression is low, while K(IR)2.2 is abundant at the membrane. The myogenic response and K+-induced dilation in cerebral arteries are unaffected by the absence of K(IR)2.1. Brain perfusion remains unchanged in K(IR)2.1 knockout mice, as assessed by arterial spin-labeling MRI.