Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus.
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.
Thompson
Roger J
RJ
Department of Psychiatry and Brain Research Centre, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. rj.thompson@ucalgary.ca
Jackson
Michael F
MF
Olah
Michelle E
ME
Rungta
Ravi L
RL
Hines
Dustin J
DJ
Beazely
Michael A
MA
MacDonald
John F
JF
MacVicar
Brian A
BA
D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000502:physiology*; D003712:Dendrites / Q000502:physiology; D054351:Electrical Synapses / Q000502:physiology; D004827:Epilepsy / Q000503:physiopathology; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission
D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate; C479936:pannexin 1, rat; D000255:Adenosine Triphosphate; D002118:Calcium