Abstract
Intracellular recordings made from pyramidal neurons in the rat hippocampal CA1 region revealed that superfusion with oxygen and glucose-deprived medium (in vitro ischemia) produced a rapid depolarization after 6 min of exposure. When oxygen and glucose were reintroduced immediately after the rapid depolarization, the membrane depolarized further, reaching 0 mV (membrane dysfunction) in CA1 pyramidal neurons. To assess effects of proteoglycans on the membrane dysfunction produced by in vitro ischemia, changes in cytoplasmic Ca2+ concentration ([Ca2+]i) from Fura-2/AM loaded slices were also measured. Pretreatment of the slices with polysaccharide lyases acting on heparan sulfate (heparinase II and III, 1 U/ml) or chondroitin sulfate (chondroitinase ABC, 20 mU/ml) did not prevent the generation of the rapid depolarization and the corresponding rapid increase in [Ca2+]i in the pyramidal neurons. In contrast, the membrane was significantly restored toward the preexposure potential levels after the reintroduction. Heparinase II and III, but not chondroitinase ABC, prolonged the latencies of both the rapid depolarization and the rapid increase in [Ca2+]i, and completely restored the [Ca2+]i to the preexposure level after the reintroduction. These results suggest that heparan sulfate and chondroitin sulfate proteoglycan may contribute, at least partially, to the generation of the membrane dysfunction of the CA1 pyramidal neurons produced by in vitro ischemia. [J Physiol Sci. 2007;57 Suppl:S114]
