TY - JOUR

T1 - KIR channels tune electrical communication in cerebral arteries

AU - Sancho, Maria

AU - Samson, Nina C

AU - Hald, Bjorn O

AU - Hashad, Ahmed M

AU - Marrelli, Sean P

AU - Brett, Suzanne E

AU - Welsh, Donald G

N1 - © The Author(s) 2016.

PY - 2017/6

Y1 - 2017/6

N2 - The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K(+) channels (KIR) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K(+) conductances had no attenuating effect, the exception being Ba(2+) blockade of KIR Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba(2+)-sensitive KIR current comprised of KIR2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of KIR channels exist and consistent with this idea, a robust Ba(2+)-sensitive KIR2.1/2.2 current was observed in endothelial cells. When both KIR currents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K(+) channels. In summary, this study shows that two KIR populations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.

AB - The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K(+) channels (KIR) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K(+) conductances had no attenuating effect, the exception being Ba(2+) blockade of KIR Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba(2+)-sensitive KIR current comprised of KIR2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of KIR channels exist and consistent with this idea, a robust Ba(2+)-sensitive KIR2.1/2.2 current was observed in endothelial cells. When both KIR currents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K(+) channels. In summary, this study shows that two KIR populations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.

U2 - 10.1177/0271678X16662041

DO - 10.1177/0271678X16662041

M3 - Journal article

C2 - 27466375

VL - 37

SP - 2171

EP - 2184

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 6

ER -