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Journal of Lipid Research, Vol. 46, 2580-2585, December 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Inhibitory effect of ganglioside GD1b on K⁺ current in hippocampal neurons and its involvement in apoptosis suppression

Xuesong Chen^1,*, Shaopeng Chi^1,, Mingna Liu^,, Wei Yang, Taotao Wei^*, Zhi Qi^2, and Fuyu Yang^2,*

^* National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People's Republic of China
Graduate School of the Chinese Academy of Sciences, Beijing 100039, People's Republic of China

Published, JLR Papers in Press, October 1, 2005. DOI 10.1194/jlr.M500252-JLR200

¹ X. Chen and S. Chi contributed equally to this work.

² To whom correspondence should be addressed. e-mail: qizhi{at}sun5.ibp.ac.cn (Z.Q.); yangfy{at}sun5.ibp.ac.cn (F.Y.)

Gangliosides are endogenous membrane components enriched in neuronal cells. They have been shown to play regulatory roles in many cellular processes. Here, we show for the first time that ganglioside GD1b plays an antiapoptotic role in cultured hippocampal neurons. GD1b inhibited the voltage-dependent outward delayed rectifier current (I_K) but not the transient outward A-type current in a dose-dependent manner, with an IC₅₀ value of 15.2 µM. This effect appears to be somehow specific, because GD1b, but not GM1, GM2, GM3, GD1a, GD3, or GT1b, was effective in inhibiting I_K. Intracellular application of staurosporine (STS; 0.1 µM) resulted in rapid activation of I_K, which was partially reversed upon addition of the K⁺ channel blocker tetraethylammonium (TEA; 5 mM) and GD1b (10 µM). Furthermore, GD1b (10 µM) attenuated STS-induced neuronal apoptosis by nearly the same amount as 5 mM TEA. In addition, GD1b suppressed the apoptosis-associated caspase 3 activation that was activated by STS.

Collectively, these findings suggest that GD1b plays an antiapoptotic role in cultured hippocampal neurons through its inhibitory effect on the I_K and caspase activity.

Abbreviations: DEVD-MCA, acetyl-Asp-Glu-Val-Asp--(4-methylcoumaryl-7-amide); DIV, days in vitro; I_A, transient outward A-type current; I_K, voltage-dependent outward delayed rectifier K⁺ current; STS, staurosporine; TEA, tetraethylammonium; TUNEL, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling

Supplementary key words ion channel regulation • potassium channel • sphingolipids • lipid rafts/microdomains

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