Alteration of ryanodine receptors after 6-hour hemispheric ischemia in the gerbil brain

Abstract

In order to evaluate the influence of cerebral ischemia on the intracellular channels of calcium-induced calcium release (CICR), the alterations of ryanodine receptor binding sites and local cerebral blood flow (LCBF) were examined at 6 hours after occlusion of the right common carotid artery in the gerbil brain. The autoradiographic method developed in our laboratory enabled us to measure both parameters within the same brain. Animals attaining ischemic scores of more than 5, as assessed at 1 hour after the occlusion, were used. LCBF was measured at 6 hours after the occlusion by the [¹⁴C] iodoantipyrine method. The ryanodine receptor binding sites were evaluated in vitro using [³H] ryanodine as a specific ligand. LCBF was significantly reduced in most of the cerebral regions on the occluded side. In contrast, a significant reduction in ryanodine binding sites was noted only in the hippocampus CAl on the occluded side. On the other hand, the ryanodine receptor immunoreactivity which was examined with a specific antibody against ryanodine receptor protein, did not reveal any differences between the ischemia and sham groups on both sides, suggesting that the ryanodine receptors may not underego significant morphological degradation. These findings indicate that the suppression of ryanodine binding in the hippocampus CAl may be attributable to a regionally specific perturbation of CICR. Such perturbation may be closely associated with the pathophysiological mechanism of selective ischemic vulnerability of this region.