Inhibitory effect of ganglioside GD1b on K+current in hippocampal neurons and its involvement in apoptosis suppression
Journal of Lipid Research
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 IC 50 value of 15.2 M. This effect appears to be somehow specific,
... ow 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 M) 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 M). Furthermore, GD1b (10 M) 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. -Chen, X., S. Inhibitory effect of ganglioside GD1b on K ؉ current in hippocampal neurons and its involvement in apoptosis suppression. J. Lipid Res. 2005. 46: 2580-2585. Supplementary key words ion channel regulation • potassium channel • sphingolipids • lipid rafts/microdomains 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 ϩ current; STS, staurosporine; TEA, tetraethylammonium; TUNEL, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling.