Role of presynaptic HCN channels in regulating synaptic transmission in the entorhinal cortex
Saturday, Nov 13, 2010, 1:00 PM - 2:00 PM
, R. LUJAN
, M. M. SHAH
Sch. of Pharmacy, Univ. of London, London, United Kingdom;
Univ. de Castilla-La Mancha, Albacete, Spain
The function of voltage-gated ion channels depends on their subcellular localization, biophysical properties and expression levels. It is established that Hyperpolarization-activated Cation Non-selective (HCN) channels are present on distal dendrites of pyramidal neurons in hippocampus and cortex. Emerging evidence suggests that these channels may also be present pre-synaptically in these areas. In support, our recent work shows that excitatory synaptic transmission is elevated in the entorhinal cortex (EC) of HCN1 null mice, indicating that HCN1 channels may be present pre-synaptically . In this study, we have further investigated this possibility.
Whole-cell voltage-clamp recordings were obtained from EC layer III pyramids of adult HCN1 null mice and their wild-type littermates. Pharmacological block of HCN channels with ZD7288 (15 µM) doubled dendritic and somatic miniature excitatory post-synaptic current (mEPSC) frequency in wild-types while having no effect on HCN1-/-. In addition, the mEPSC frequency recorded from HCN1-/- neurons was 2-4 times greater than wild-types. Surprisingly, we found that mEPSC frequency in HCN1-/- had a greater dependence on extracellular calcium concentration, suggesting that reducing HCN channel expression enhanced Ca2+ influx into presynaptic terminals. To explore this further, we tested the effects of different voltage-gated calcium channel antagonists on mEPSC frequency. Interestingly, the results suggested that only T-type calcium channel blockers prevented the enhancement of mEPSC frequency induced by ZD7288. These findings, thus, suggest a novel function of HCN1 subunits.
 Huang, Z., Walker, M. C. & Shah, M. M. (2009). "Loss of dendritic HCN1 subunits enhances cortical excitability and epileptogenesis." J Neurosci 29(35): 10979-88.
MRC NIA, G0700369
Wellcome Trust., WT087363MA
[Authors]. [Abstract Title]. Program No. XXX.XX. 2010 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online.
2010 Copyright by the Society for Neuroscience all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
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