Hydrogen sulfide regulates intracellular pH in rat primary cultured glia cells

• Published in: Neuroscience research Vol. 66; no. 1; pp. 92 - 98
• Main Authors: Lu, Ming, Choo, Chooi Hoong, Hu, Li-Fang, Tan, Boon Hian, Hu, Gang, Bian, Jin-Song
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 2010
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Acidification; Air Pollutants - pharmacology; Analysis of Variance; Animals; Animals, Newborn; Cells, Cultured; Cerebral Cortex - cytology; Chloride-Bicarbonate Antiporters - metabolism; Dose-Response Relationship, Drug; Glia cells; H 2S; Humans; Hydrogen Sulfide - pharmacology; Hydrogen-Ion Concentration - drug effects; Intracellular Fluid - drug effects; Na +-independent Cl −/HCO 3− exchanger; Na +/H + exchanger; Neuroblastoma; Neuroglia - cytology; Neuroglia - drug effects; Rats; Rats, Sprague-Dawley; H 2S; Acidification; Na +-independent Cl −/HCO 3 − exchanger; Glia cells; Na +/H + exchanger
• ISSN: 0168-0102; 1872-8111
• DOI: 10.1016/j.neures.2009.09.1713

Intracellular pH (pH
i) plays an important role in the regulation of central nervous system function. In the present study, we examined whether hydrogen sulfide (H
2S), a recently recognized neuromodulator, regulates pH
i in rat primary cultured glia cells. pH
i was measured with a fluorescent sensitive dye, BCECF-AM. Activities of Cl
−/HCO
3
− exchanger and Na
+/H
+ exchanger were examined by assessing their capacities to load or extrude H
+ upon NH
4Cl pulse load. We found that NaHS, a H
2S donor, decreased pH
i in a concentration-dependent manner ranging from 10 to 200
μM in the primary cultured microglia. Blockade of the Cl
−/HCO
3
− exchanger with, 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS) or Na
+/H
+ exchanger with 5-N-methyl-N-isobutylamiloride (MIA) significantly attenuated the pH
i-lowering effect of NaHS. Moreover, NaHS significantly increased the activity of Cl
−/HCO
3
− exchanger but inhibited that of Na
+/H
+ exchanger. The pH regulatory effect of H
2S was also observed in primary cultured astrocytes, but not in SH-SY5Y neuronal cells. In conclusion, we found for the first time that H
2S induced intracellular acidification in glia cells via regulation of the activities of Cl
−/HCO
3
− exchanger and Na
+/H
+ exchanger. The present study may provide new evidence for H
2S to serve as a neuromodulator and offer a potential approach for the treatment of neurological diseases.