Activation Of Pannexin-1 Hemichannels Augments Aberrant Bursting In The Hippocampus

摘要

Pannexin-1 (Px1) is expressed at postsynaptic sites in pyramidal neurons, suggesting that these hemichannels contribute to dendritic signals associated with synaptic function. We found that, in pyramidal neurons, N-methyl-D-aspartate receptor (NMDAR) activation induced a secondary prolonged current and dye flux that were blocked with a specific inhibitory peptide against Pxl hemichannels; knockdown of Pxl by RNA interference blocked the current in cultured neurons. Enhancing endogenous NMDAR activation in brain slices by removing external magnesium ions (Mg~(2+)) triggered epileptiform activity, which had decreased spike amplitude and prolonged interburst interval during application of the Pxl hemichannel blocking peptide. We conclude that Pxl hemichannel opening is triggered by NMDAR stimulation and can contribute to epileptiform seizure activity.