Although excitotoxic cell death is usually considered a Ca 2+ -dependent process, in certain neuronal systems there is strong evidence that excitotoxic cell death is independent of Ca 2+ and is instead remarkably dependent on extracellular Cl − . We have shown (in isolated chick embryo retina) that at least some of the lethal Cl − entry is through GABA and glycine receptors. Here we show that when all the GABA and glycine receptors are blocked by using an appropriate cocktail of inhibitors, agonist-induced excitotoxic cell death can be completely prevented. To determine if ligand-gated Cl − channels contribute to excitotoxic cell death in other neurons, we examined KA-induced cell death in cultured rat cerebellar granule cells. GABA receptor blockade with either a competitive or noncompetitive antagonist provides complete neuroprotection. KA stimulates Cl − uptake by the granule cells, and this is blocked by the GABA antagonists. Granule cell cultures take up ( 3 H)GABA and release it in response to KA treatment. A subpopulation of neurons in the cultures is shown to have GAD and high concentrations of GABA, and this presumably is the source of the GABA that leads to receptor activation and lethal Cl − entry. Finally, we show that retinal cell death due to 1 h of simulated ischemia (combined oxygen and glucose deprivation) is completely prevented by blocking the inhibitory receptors. These results indicate that, paradoxically, excitotoxic cell death is completely dependent on activation of inhibitory receptors, in at least some neuronal systems, and this pathological process may contribute to disease.
Experimental Neurology – Elsevier
Published: Nov 1, 1999
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera