New Modes of GPCR Signalling
New Modes of GPCR Signalling
New Modes of GPCR Signalling
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Effects <strong>of</strong> ZD7288 on Long-Term Potentiation at Perforant Pathway(PP)<br />
Fibers - CA3 Region Synapse Pathway in Rat Hippocampus in Vivo<br />
Xulin Xu1, Min Zheng1, 2 , Lian-Jun Guo1*,<br />
1Department <strong>of</strong> Pharmacology, Tongji Medical College, Huazhong University <strong>of</strong><br />
Science & Technology, 13 Hongkong Road, Wuhan 430030, China.<br />
2 Department <strong>of</strong> Pharmacology,Xianning College, 88 Xianning Thoroughfare,<br />
Xianning 437100, China.<br />
Aim: To investigate effects <strong>of</strong> a hyperpolarization-activated cyclic nucleotide-gated cation<br />
(HCN) channel specific blocker ZD7288 to LTP at perforant pathway (PP) fibers-CA3 region<br />
synapse pathway in rat hippocampus. Methods: The field excitatory postsynaptic potentials<br />
(fEPSPs) <strong>of</strong> PP—CA3 region synapse in rats was recorded by using the extracellular<br />
recording techniques in vivo. Tetanic stimulation (TS; consisted <strong>of</strong> 50 trains at 0.5 Hz each<br />
composed <strong>of</strong> 4 pulses at 500Hz) was administrated to observe the induction and maintenance <strong>of</strong><br />
LTP. We observed the effects <strong>of</strong> ZD7288 on the induction and sustain <strong>of</strong> LTP in PP—CA3<br />
pathway. Simultaneously, the synapse ultrastructural at hippocampal CA3 region was observed<br />
by transmission electron microscope. Results: ①The fEPSPs amplitude persistently stabilized<br />
at 281.8 ± 6.6% <strong>of</strong> baseline in 90min after giving tetanic stimulation <strong>of</strong> PP fibers in<br />
LTP-induction group and significantly higher than that in control group(97.4 ±1.8%)(P < 0.01).<br />
② Local administration <strong>of</strong> ZD7288 100nmol/L before TS, the induction <strong>of</strong> LTP was obviously<br />
suppressed. The relative fEPSPs amplitudes in each time point were all significantly lower than<br />
that in LTP-induction group (n=10, P 0.05).③Local administration <strong>of</strong> ZD7288<br />
100nmol/L at 30min after TS, the fEPSPs amplitudes at each time point in 1h after<br />
administration were all significantly lower than LTP-induction group (n=10, P < 0.01), and the<br />
average values were 95.8 ± 6.4% near to control group(P > 0.05). ④ In the LTP induction group,<br />
the cell ultramicrostructure at hippocampus CA3 region showed that there were many synaptic<br />
vesicles in presynaptic endochylema and many synaptic vesicles like thyrsiform occurred in the<br />
presynaptic end in this synapses. ⑤In the ZD7288 -TS group, the cell ultramicrostructure at<br />
hippocampus CA3 region showed that there were no synaptic glomerulus and the synaptic<br />
vesicles were decreased compared with the LTP induction group. Conclusions: It is suggest<br />
that ZD7288 could produce inhibitive effects on the induction and maintenance <strong>of</strong> long-term<br />
potentiation at PP-CA3 synapse pathway and this action may be associated with altering the<br />
release <strong>of</strong> neurotransmitter.<br />
Key Words: ZD7288; HCN channel; PP—CA3 pathway ; LTP<br />
Acknowledgments: This work was supported by grants from the National Natural Science<br />
Foundation <strong>of</strong> China (NSFC, No. 30772559) to Lianjun Guo<br />
Author: Xulin Xu , Email: xulinxu@yahoo.com , Tel: 027-83691762;<br />
* Correspondence author: Tel: +86 27 83691762, E-mail: gljyl@yahoo.com.cn
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