T.-F.M, L.Z, and Y.W contributed equally to this work.
A selective M1 and M3 receptor antagonist, penehyclidine hydrochloride, prevents postischemic LTP: Involvement of NMDA receptors
Article first published online: 24 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 67, Issue 12, pages 865–874, December 2013
How to Cite
Ma, T.-F., Zhou, L., Wang, Y., Qin, S.-J., Zhang, Y., Hu, B., Yan, J.-Z., Ma, X., Zhou, C.-H. and Gu, S.-L. (2013), A selective M1 and M3 receptor antagonist, penehyclidine hydrochloride, prevents postischemic LTP: Involvement of NMDA receptors. Synapse, 67: 865–874. doi: 10.1002/syn.21693
- Issue published online: 15 OCT 2013
- Article first published online: 24 JUL 2013
- Accepted manuscript online: 29 JUN 2013 07:02AM EST
- Manuscript Accepted: 19 JUN 2013
- Manuscript Received: 15 APR 2013
- Key Laboratory for Brain Disease Bioinformation of Jiangsu Province. Grant Number: Jsbl1206
- Exclusive funds of talent in Xuzhou Medical College. Grant Number: 2012KJZ21
- Zhen Xing Project of XZMC
- Priority Academic Program Development of Jiangsu Higher Education Institutions, China
- NMDA receptor;
- muscarinic receptor;
- hippocampus slice
Our previous and other studies have confirmed that a selective M1 and M3 receptor antagonist, Penehyclidine hydrochloride (PHC), has neuroprotection activity in cerebral ischemia. However, the precise mechanisms of protection of PHC are still elusive. In this study we analyzed PHC-mediated neuroprotection on a model of brain ischemia (oxygen and glucose deprivation), named postischemic LTP (i-LTP). We found that the activation of NMDA receptor was required for the induction of i-LTP. Compared with scopolamine, PHC could prevent it due to selectively blocking M1 receptor, not M2 receptor, to decrease NMDAR activation. Our findings further showed that the inhibition of SK2 channels occluded the prevention of PHC on NMDAR activation. Furthermore, we confirmed that PHC exerted its roles through directly disinhibition of SK2 channels by blocking M1 receptor and subsequent restricting PKC activation. Moreover, our studies further revealed the critical roles of SK2 channels in i-LTP. Thus, the mechanisms of PHC in brain protection may be involved in suppression of NMDAR by regulation of SK2 channels. Our results obtained in effects of PHC on i-LTP further provided a better understanding of the therapy strategy during stroke and identified potential therapeutic targets to prevent development of ischemia. Synapse 67:865–874, 2013. © 2013 Wiley Periodicals, Inc.