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

• Published in: Journal of cerebral blood flow and metabolism 2022-09, Vol.42 (9), p.271678X221093432-1706
• Main Authors: Kowalewska, Paulina M, Fletcher, Jacob, Jackson, William F, Brett, Suzanne E, Kim, Michelle SM, Mironova, Galina Yu, Haghbin, Nadia, Richter, David M, Tykocki, Nathan R, Nelson, Mark T, Welsh, Donald G
• Format: Article
• Language: English
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X221093432

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 ) channels are thought to be a key determinant. To elucidate the role of K 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 2.1 knockout mice. Patch-clamp electrophysiology revealed a robust Ba -sensitive inwardly rectifying K current in cerebral arterial myocytes irrespective of K 2.1 knockout. Immunolabeling clarified that K 2.1 expression was low in SMCs while K 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 mice, as assessed with arterial spin-labeling MRI. We confirmed these findings in superior epigastric arteries and implicated K 2.2 as more functionally relevant in SMCs. Together, these results suggest that subunits other than K 2.1 play a significant role in setting native current in SMCs and driving arterial tone.