Inhibition of Post-Synaptic Kv7-KCNQ-M Channels Facilitates Long-Term Potentiation in the HippocampusReport as inadecuate




Inhibition of Post-Synaptic Kv7-KCNQ-M Channels Facilitates Long-Term Potentiation in the Hippocampus - Download this document for free, or read online. Document in PDF available to download.

Activation of muscarinic acetylcholine receptors mAChR facilitates the induction of synaptic plasticity and enhances cognitive function. In the hippocampus, M1 mAChR on CA1 pyramidal cells inhibit both small conductance Ca2+-activated KCa2 potassium channels and voltage-activated Kv7 potassium channels. Inhibition of KCa2 channels facilitates long-term potentiation LTP by enhancing Ca2+calcium influx through postsynaptic NMDA receptors NMDAR. Inhibition of Kv7 channels is also reported to facilitate LTP but the mechanism of action is unclear. Here, we show that inhibition of Kv7 channels with XE-991 facilitated LTP induced by theta burst pairing at Schaffer collateral commissural synapses in rat hippocampal slices. Similarly, negating Kv7 channel conductance using dynamic clamp methodologies also facilitated LTP. Negation of Kv7 channels by XE-991 or dynamic clamp did not enhance synaptic NMDAR activation in response to theta burst synaptic stimulation. Instead, Kv7 channel inhibition increased the amplitude and duration of the after-depolarisation following a burst of action potentials. Furthermore, the effects of XE-991 were reversed by re-introducing a Kv7-like conductance with dynamic clamp. These data reveal that Kv7 channel inhibition promotes NMDAR opening during LTP induction by enhancing depolarisation during and after bursts of postsynaptic action potentials. Thus, during the induction of LTP M1 mAChRs enhance NMDAR opening by two distinct mechanisms namely inhibition of KCa2 and Kv7 channels.



Author: Milos M. Petrovic, Jakub Nowacki, Valeria Olivo, Krasimira Tsaneva-Atanasova, Andrew D. Randall, Jack R. Mellor

Source: http://plos.srce.hr/



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