Cell swelling following recovery from acidification in C6 glioma cells: an in vitro model of postischemic brain edema.
Two consequences of cerebral ischemia are cell acidification and cytotoxic edema. To test the possibility that Na+/H+ exchange mediates acid-induced edema, we measured cytoplasmic pH (pHi) and cell volume changes in C6 glioma cells that were artificially acid-loaded using weak electrolytes. pHi was monitored fluorimetrically with 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein. Upon acidification with sodium propionate, pHi dropped to 6.74 +/- 0.05 (n = 25), and then recovered to levels near the physiological value of 7.23 +/- 0.02 (n = 13). Cell volume, measured by electronic sizing, increased concomitantly by approximately 50% in sodium propionate solution. Both pHi recovery and cell swelling were Na+-dependent, amiloride-sensitive, and inhibited at pHo less than 6.0. These results demonstrate that in vitro: (1) intracellular acidification can lead to cell swelling, and (2) pHi recovery and the concomitant cell swelling are likely mediated by Na+/H+ exchange. These mechanisms may be related to postischemic cytotoxic glial edema.
Division of Neurology, Hospital for Sick Children, Toronto, Ont., Canada.
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Jakubovicz
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Grinstein
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Klip
D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D002460:Cell Line; D003593:Cytoplasm / Q000032:analysis; D005910:Glioma / Q000473:pathology*; D006863:Hydrogen-Ion Concentration; D051381:Rats; D012964:Sodium / Q000032:analysis; D013050:Spectrometry, Fluorescence
D012964:Sodium