Autoradiographic analysis of L- and N-type voltage-dependent calcium channel binding in canine brain after global cerebral ischemia/reperfusion.
Binding of antagonists to L- and N-type voltage-dependent calcium channels (VDCC) was measured in canine brain following global ischemia and reperfusion. Ischemia was induced by 10 min cardiac arrest, followed by restoration of spontaneous circulation for periods of up to 24 h. Binding of [3H]PN200-110 and [125I]omega-conotoxin GVIA to frozen sections from hippocampus, striatum, parietal cortex and temporal cortex was analyzed using quantitative receptor autoradiography. The binding patterns of the two radioligands were similar in cortex and striatum, but differed in hippocampus. In the latter tissue, [125I]omega-conotoxin GVIA binding was dense over synaptic regions, especially the presynaptic polymorph layer of the dentate gyrus, but was virtually absent over cell body layers. In contrast, [3H]PN200-110 binding was more homogenously distributed, with highest binding in the molecular layer of the dentate gyrus. The binding of [125I]omega-conotoxin GVIA was not different from sham controls at any time point following cardiac arrest. [3H]PN200-110 binding was decreased in each region immediately following ischemia, recovering within 30 min of recirculation. These findings are in contrast to earlier findings of rapid increases in L-type VDCC binding to membrane fractions obtained from cortex and striatum in this model, and suggest that the previously detected increases may be due to a redistribution of channels from subcellular compartments to the plasma membrane during ischemia.
Perry
D C
DC
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037.
Wei
H
H
Rosenthal
R E
RE
Fiskum
G
G
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D004285:Dogs; D005260:Female; D011869:Radioligand Assay; D015427:Reperfusion Injury / Q000378:metabolism*
D015220:Calcium Channels