ALTERED FUNCTION OF INWARD RECTIFIER POTASSIUM CHANNELS IN CEREBROVASCULAR SMOOTH-MUSCLE AFTER ISCHEMIA REPERFUSION/

Background and Purpose-Several recent studies have demonstrated that i nward rectifier potassium channels (K(ir)s) are located on vascular sm ooth 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 rec tifier potassium channels is altered after ischemia/reperfusion (I/R). Methods-Temporary (2-hour) focal ischemia was induced in male Long-Ev ans 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 diame ters for contralateral (control) and ipsilateral (I/R) MCAs were not s ignificantly different (215+/-4 mu m and 211+/-5 mu m [n=6 and n=7], r espectively). 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). Ac tivation of the K(ir)s in I/R MCAs produced a dilation of only 11+/-3% (n=8; P<0.001 compared with control). BaCl2, (75 mu mol/L), a concent ration-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 administ ration of uridine triphosphate (10 mu mol/L) produced similar dilation s in both groups (32+/-5% for sham [n=4] and 33+/-2% for I/R [n=4]), i ndicating that dilator function in general was not altered in I/R vess els. Conclusions-We conclude that K-ir function is altered after I/R. The K-ir altered function is Likely to exacerbate the brain injury occ urring after I/R.