Relationship between Inward Rectifier Potassium Current Impairment and Brain Injury after Cerebral Ischemia/Reperfusion

Abstract

Functional alterations of barium-sensitive potassium inward rectifier (KIR) current, which is involved in the vasodilation of middle cerebral arteries (MCA) in rat brain, have been described during brain ischemia/reperfusion (I/R). The authors investigate the effects of I/R on KIR current recorded in isolated myocytes from MCA of control rats and from contralateral and ipsilateral MCA of ischemic rats by the whole-cell patch-clamp technique, and the relationship between its alteration and the severity of brain injury. The vascular smooth muscle cells exhibited similar morphologic features in all conditions, and the KIR was present in the three groups of myocytes, exhibiting a characteristic inward rectification and a normal external potassium dependence. The KIR density was significantly reduced in cell of MCA ipsilateral to occlusion with a maximum at -135 mV, whereas there was no difference between control and contralateral cells. This alteration in KIR density in occluded MCA was significantly correlated with severity of brain injury and brain edema. These results suggest that the alteration of KIR density in MCA myocytes after I/R and the consecutive impaired dilation of MCA may contribute to aggravation of the brain injury.

Involvement of Thrombolysis in Recombinant Tissue Plasminogen Activator-Induced Cerebral Hemorrhages and Effect on Infarct Volume and Postischemic Endothelial Function

“…17 Physiological parameters (temperature, mean arterial pressure, arterial blood pH, PaO 2 , and PaCO 2 ) were controlled throughout the experiments. Subsequently, the right jugular vein was isolated and cannulated with a polyethylene catheter (24-gauge) for intravenous rtPA infusion.…”

“…Total, cortical, and subcortical infarct volumes and hemispheric volumes (mm 3 ) were obtained by the use of numerical integration of the respective calculated areas for all sections per animal. 17 A corrected volume for edema was calculated with the use of the following equation: Corrected Infarct VolumeϭInfarct VolumeϪ(Right Hemisphere VolumeϪLeft Hemisphere Volume).…”

Nitric Oxide Donor Sodium Nitroprusside Dilates Rat Small Arteries by Activation of Inward Rectifier Potassium Channels

“…First information about the existence of K IR channels in small artery preparations was reported by Edwards. 4,5 Thereafter, direct measurements of ion currents in vascular smooth muscle cells demonstrated the existence of K IR currents in cerebral, 6,7 coronary, 8 -10 and renal 11 small arteries and in the hepatic artery. 12 Recently, it has been demonstrated by electrophysiological and molecular biological techniques that K IR 2.1 channels underlie the K IR currents in coronary, cerebral, and mesenteric small artery smooth muscle cells.…”

Delayed Cerebrovascular Protective Effect of Lipopolysaccharide in Parallel to Brain Ischemic Tolerance

“…The ostium of the right MCA was occluded intraluminally as previously described (Bastide et al, 1999). The right carotid arteries were exposed through a midline cervical incision and the common carotid and external carotid arteries were ligated with a silk suture.…”

“…Loss of vascular tone, diminished responsiveness to the vasoconstrictor effect of 5-hydroxytryptamine (5-HT), abolition of the endotheliumdependent relaxation in response to acetylcholine, and diminished distensibility have been reported (Cipolla et al, 1997;Rosenblum et al, 2000). Deleterious effects of ischemia-reperfusion also occur in the smooth muscle of the occluded cerebral artery where alterations of bariumsensitive K + inward rectifier (KIR) channel currents, which are involved in the relaxation of cerebral arteries, have been described (Bastide et al, 1999;Marelli et al, 1998). By their consequences for cerebral blood flow, these vascular abnormalities could affect, in turn, the neuronal function.…”