High Glucose Enhances Isoflurane-Induced Neurotoxicity by Regulating TRPC-Dependent Calcium Influx

• Published in: Neurochemical research 2017-04, Vol.42 (4), p.1165-1178
• Main Authors: Liu, ZhongJie, Ma, ChangQing, Zhao, Wei, Zhang, QingGuo, Xu, Rui, Zhang, HongFei, Lei, HongYi, Xu, ShiYuan
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cell Biology; Cell Line, Tumor; Cells, Cultured; Drug Synergism; Glucose - toxicity; Hippocampus - drug effects; Hippocampus - metabolism; Humans; Imidazoles - pharmacology; Isoflurane - toxicity; Mice; Mice, Inbred C57BL; Neurochemistry; Neurology; Neurons - drug effects; Neurons - metabolism; Neurosciences; Original Paper; TRPC Cation Channels - antagonists & inhibitors; TRPC Cation Channels - biosynthesis
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-016-2152-1

Isoflurane is a commonly used inhalational anesthetic that can induce neurotoxicity via elevating cytosolic calcium (Ca 2+ ). High glucose regulates the expression of a family of non-selective cation channels termed transient receptor potential canonical (TRPC) channels that may contribute to Ca 2+ influx. In the present study, we investigated whether high glucose enhances isoflurane-induced neurotoxicity by regulating TRPC-dependent Ca 2+ influx. First, we evaluated toxic damage in mice primary cultured hippocampal neurons and human neuroblastoma cells (SH-SY5Y cells) after hyperglycemia and isoflurane exposure. Next, we investigated cytosolic Ca 2+ concentrations, TRPC mRNA expression levels and tested the effect of the TRPC channel blocker SKF96365 on cytosolic Ca 2+ levels in cells treated with high glucose or/and isoflurane. Finally, we employed knocked down TRPC6 to demonstrate the role of TRPC in high glucose-mediated enhancement of isoflurane-induced neurotoxicity. The results showed that high glucose could enhance isoflurane-induecd toxic damage in primary hippocampal neurons and SH-SY5Y cells. High glucose enhanced the isoflurane-induced increase of cytosolic Ca 2+ in SH-SY5Y cells. High glucose elevated TRPC mRNA expression, especially that of TRPC6. SKF96365 and knock down of TRPC6 were able to inhibit the high glucose-induced increase of cytosolic Ca 2+ and decrease isoflurane-induced neurotoxicity in SH-SY5Y cells cultured with high glucose. Our findings indicate that high glucose could elevate TRPC expression, thus increasing Ca 2+ influx and enhancing isoflurane-induced neurotoxicity.