Hypoxia on hippocampal slices from mice deficient in dystrophin (mdx) and isoforms (mdx(3cv))

Slices from control C57, mdx, and mdx(3cv) mice were made hypoxic until bot h field excitatory postsynaptic potential (fEPSP) and presynaptic afferent volley (AV) disappeared (H1). After reoxygenation and recovery of fEPSP, a second and longer hypoxic test (H2) lasted 3 minutes beyond the time requir ed to block AV. When slices were kept in 10 mmol/L glucose, H1 abolished AV 37 and 19% earlier in slices from mdx and mdx(3cv) mutants than in control slices (where ill = 12 +/- 4.6 minutes, mean +/- SD). During H2 or when sl ices were kept in 4 mmol/L glucose, AV vanished even more quickly, but the times to block did not differ significantly between slices from controls an d mutants. After reoxygenation, AV fully recovered in most slices. Rates of blockade of fEPSPs were comparable in all slices, and most fEPSPs recovere d fully after H1. But even in the presence of 10 mmol/L glucose, the second hypoxia suppressed fEPSPs irreversibly in some slices: 2 of 10 from contro l, 3 of 7 from mdx, and 1 of 6 from mdx(3cv) mice. Most slices in 4 mmol/L glucose showed no recovery at all: six of seven from control, three of five from mdx, and four of five from mdx(3cv) mice. Thus, slices from mdx mice were more susceptible than other slices to irreversible hypoxic failure whe n slices were kept in 10 mmol/L glucose, but they were less susceptible tha n other slices when kept in 4 mmol/L glucose. In conclusion, the lack of fu ll-length dystrophin (427 kDa) predisposes to quicker loss of nerve conduct ion in slices from mdx and mdx(3cv) mutants and improved posthypoxic recove ry of fEPSPs in 4 mmol/L glucose in slices from mdx but not mdx(3cv) mutant s, perhaps because the 70-kDa and other C-terminal isoforms are still prese nt in mdx mice.