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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:746.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

High Glucose Enhances Transient Receptor Potential Channel Canonical Type 6–Dependent Calcium Influx in Human Platelets via Phosphatidylinositol 3-Kinase–Dependent Pathway

Daoyan Liu; Alexandra Maier; Alexandra Scholze; Ursula Rauch; Ulrike Boltzen; Zhigang Zhao; Zhiming Zhu; Martin Tepel

From the Med. Klinik, Department of Nephrology (D.L., A.M., A.S., M.T.), Charité Campus Benjamin Franklin, Berlin, Germany; the Center for Hypertension and Metabolic Diseases (D.L., Z.Z., Z.Z.), Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing, China; and the Med. Klinik, Department of Cardiology (U.R., U.B.), Charité Campus Benjamin Franklin, Berlin, Germany.

Correspondence to Dr Zhiming Zhu, Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology, Daping Hospital, Third Military Medical University, Chongqing, China. E-mail zhuzming{at}mail.dph-fsi.com

Background— Transient receptor potential canonical type 6 (TRPC6) channels mediating 1-oleoyl-2-acetyl-sn-glycerol (OAG)–induced calcium entry have been identified on human platelets. In the present study we tested the hypothesis that hyperglycemia increases the expression of TRPC6 channels.

Methods and Results— Platelets from healthy control subjects and patients with type 2 diabetes mellitus were incubated with glucose and calcium influx was measured using the fluorescent dye technique. TRPC channel protein expression was investigated using immunofluorescence and fluorescence microscopy of single platelets. Administration of 25 mmol/L glucose significantly enhanced the OAG-induced calcium influx, which was attenuated by inhibitors of the phosphatidylinositol 3-kinase, wortmannin or LY294002. The glucose-enhanced and OAG-induced calcium influx was concentration- and time-dependent. Glucose significantly increased the TRPC6 protein expression in platelets to 131±12% (n=33; P<0.05), whereas the expression of TRPC1, TRPC3, TRPC4, or TRPC5 were unchanged. The glucose-induced TRPC6 expression was significantly attenuated in the presence of wortmannin or LY294002. Platelets from patients with type 2 diabetes mellitus showed increased TRPC6 expression compared to nondiabetic individuals (P<0.05).

Conclusion— The study indicates that high glucose increases TRPC6 channel protein expression on the platelet surface which is mediated by a phosphatidylinositol 3-kinase–dependent pathway.

We tested the hypothesis that hyperglycemia increases transient receptor potential canonical type 6 (TRPC6) channel expression and 1-oleoyl-2-acetyl-sn-glycerol (OAG)–induced calcium entry in human platelets. Glucose significantly enhanced the OAG-induced calcium influx and TRPC6 expression, which was attenuated by inhibitors of the phosphatidylinositol 3-kinase, wortmannin or LY294002.

Key Words: platelet • transient receptor potential channel canonical type 6 • signal transduction • diabetes • phosphatidylinositol 3-kinase

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