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Science 322 (5907): 1555-1559

Copyright © 2008 by the American Association for the Advancement of Science

Activation of Pannexin-1 Hemichannels Augments Aberrant Bursting in the Hippocampus

Roger J. Thompson,1*{dagger} Michael F. Jackson,2 Michelle E. Olah,2 Ravi L. Rungta,1 Dustin J. Hines,1 Michael A. Beazely,2 John F. MacDonald,2 Brian A. MacVicar1{dagger}

Abstract: 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 Px1 hemichannels; knockdown of Px1 by RNA interference blocked the current in cultured neurons. Enhancing endogenous NMDAR activation in brain slices by removing external magnesium ions (Mg2+) triggered epileptiform activity, which had decreased spike amplitude and prolonged interburst interval during application of the Px1 hemichannel blocking peptide. We conclude that Px1 hemichannel opening is triggered by NMDAR stimulation and can contribute to epileptiform seizure activity.

1 Department of Psychiatry and Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada.
2 Robarts Research Institute, University of Western Ontario, London, ON N6A 5K8, Canada.

* Present address: Department of Cell Biology and Anatomy and Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive Northwest, Calgary, AB T2N 4N1, Canada.

{dagger} To whom correspondence should be addressed. E-mail: rj.thompson{at}ucalgary.ca (R.J.T.); bmacvicar{at}brain.ubc.ca (B.A.M.)

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