RT Journal Article
T1 An assessment of KIR channel function in human cerebral arteries
A1 Sancho González, María
A1 Gao, Yuan
A1 Hald, Bjorn O.
A1 Yin, Hao
A1 Boulton, Melfort
A1 Steven, David A.
A1 MacDougall, Keith W.
A1 Parrent, Andrew G.
A1 Pickering, J. Geoffrey
A1 Welsh, Donald G.
AB In the rodent cerebral circulation, inward rectifying K+ (KIR) channels set resting tone and the distance over which electrical phenomena spread along the arterial wall. The present study sought to translate these observations into human cerebral arteries obtained from resected brain tissue. Computational modeling and a conduction assay first defined the impact of KIR channels on electrical communication; patch-clamp electrophysiology, quantitative PCR, and immunohistochemistry then characterized KIR2.x channel expression/activity. In keeping with rodent observations, computer modeling highlighted that KIR blockade should constrict cerebral arteries and attenuate electrical communication if functionally expressed. Surprisingly, Ba2+ (a KIR channel inhibitor) had no effect on human cerebral arterial tone or intercellular conduction. In alignment with these observations, immunohistochemistry and patch-clamp electrophysiology revealed minimal KIR channel expression/activity in both smooth muscle and endothelial cells. This absence may be reflective of chronic stress as dysphormic neurons, leukocyte infiltrate, and glial fibrillary acidic protein expression was notable in the epileptic cortex. In closing, KIR2.x channel expression is limited in human cerebral arteries from patients with epilepsy and thus has little impact on resting tone or the spread of vasomotor responses. NEW & NOTEWORTHY KIR2.x channels are expressed in rodent cerebral arterial smooth muscle and endothelial cells. As they are critical to setting membrane potential and the distance signals conduct, we sought to translate this work into humans. Surprisingly, KIR2.x channel activity/expression was limited in human cerebral arteries, a paucity tied to chronic brain stress in the epileptic cortex. Without substantive expression, KIR2.x channels were unable to govern arterial tone or conduction.
PB American Physiological Society
SN 0363-6135
YR 2019
FD 2019-01-25
LK https://hdl.handle.net/20.500.14352/109676
UL https://hdl.handle.net/20.500.14352/109676
LA eng
NO Sancho M, Gao Y, Hald BO, Yin H, Boulton M, Steven DA, MacDougall KW, Parrent AG, Pickering JG, Welsh DG. An assessment of KIR channel function in human cerebral arteries. Am J Physiol Heart Circ Physiol. 2019. 316(4):H794-H800. doi: 10.1152/ajpheart.00022.2019.
NO Canadian Institute of Health Research
DS Docta Complutense
RD 21 ene 2026