Altered Function of Inward Rectifier Potassium Channels in Cerebrovascular Smooth Muscle After Ischemia/Reperfusion

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Abstract
Background and Purpose —Several recent studies have demonstrated that inward rectifier potassium channels (K ir s) are located on vascular smooth muscle of cerebral arteries in the rat. Activation of the K ir s dilates the arteries by relaxing the vascular smooth muscle. We tested the following hypothesis in the present study: function of inward rectifier potassium channels is altered after ischemia/reperfusion (I/R). Methods —Temporary (2-hour) focal ischemia was induced in male Long-Evans rats (3% isoflurane anesthesia) by the intraluminal filament model. After 24 hours of reperfusion, ipsilateral and contralateral middle cerebral arteries (MCAs) were harvested and mounted on micropipettes, pressurized to 85 mm Hg, and luminally perfused. Results —Resting diameters for contralateral (control) and ipsilateral (I/R) MCAs were not significantly different (215±4 μm and 211±5 μm [n=6 and n=7], respectively). Activation of the K ir s by abluminal administration of 15 mmol/L KCl to the control MCAs dilated the MCA by 34±4% (n=8). Activation of the K ir s in I/R MCAs produced a dilation of only 11±3% (n=8; P 2 (75 μmol/L), a concentration-selective inhibitor of the K ir s, significantly attenuated the dilation produced by 15 mmol/L KCl in control MCAs but not in the I/R MCAs. Endothelial-mediated dilations elicited by the luminal administration of uridine triphosphate (10 μmol/L) produced similar dilations in both groups (32±5% for sham [n=4] and 33±2% for I/R [n=4]), indicating that dilator function in general was not altered in I/R vessels. Conclusions —We conclude that K ir function is altered after I/R. The K ir altered function is likely to exacerbate the brain injury occurring after I/R.