Role for chloride but not potassium channels in apoptosis in primary rat cortical cultures.
Recent evidence suggests a predominant role for potassium (K) efflux in apoptotic cell death yet there exists controversy as to the exact nature of this involvement of K. In the present study we tested the anti-apoptotic efficacy of K channel blockers, tetraethylammonium Cl (TEA), and high extracellular K, the sodium (Na) channel blocker, tetrodotoxin (TTX) and the Cl channel blocker, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, (SITS) against staurosporine-induced apoptosis in primary rat cortical cultures. Surprisingly, we failed to observe anti-apoptotic effects with TEA, high K or TTX. We did, however, observe significant dose-dependent inhibition of apoptosis with SITS. In conclusion we demonstrate no role for K or Na in neuronal apoptosis, but rather an important role for a SITS-sensitive mechanism such as Cl.
Small
Daniel L
DL
Institute for Biological Sciences, National Research Council, Ottawa, Canada. dsmall@lexgen.com
Tauskela
Joseph
J
Xia
Zhenlei
Z
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018118:Chloride Channels / Q000494:pharmacology*; D004622:Embryo, Mammalian; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D018118:Chloride Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D019311:Staurosporine; D011188:Potassium