[Abstract Title]. - Society for Neuroscience

240. Intrinsic Membrane Properties: Modulation of Neuronal Firing Properties by Inputs
and Activity
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 240.6/E28
Topic: B.10.b. Modulation of neuronal firing properties
Support: CIHR MOP-77566
Title: TRPC channels mediate persistent activity in layer V principal neurons of the medial
entorhinal cortex
Authors: *Z. ZHANG, A. REBOREDA, A. ALONSO, P. A. BARKER, P. SEGUELA;
Neurol. & Neurosurg., Montreal Neurolog. Inst., Montreal, QC, Canada
Abstract: Principal neurons in layer V of the rat medial entorhinal cortex (MEC) generate selfsustained
plateau potentials and persistent spiking following the application of a brief
suprathreshold excitatory stimulus in the presence of the muscarinic receptor agonist carbachol
(CCh). Plateau potentials and persistent firing activity, non-synaptic mechanisms of information
storage contributing to working memory, have been shown to be mediated by a Ca2+ dependent,
non-selective cation current (Ican). However the identity of the channel(s) that carry Ican in layer
V MEC neurons is unknown. In this study, we investigated the molecular identity of the channels
mediating CCh-evoked persistent activity using whole-cell patch clamp recordings in rat layer V
MEC neurons in acute brain slices. Our data indicate that compounds that block phospholipase C
(PLC) activation and TRP channels inhibited plateau potential and persistent activity in layer V
neurons. U73122, a PLC blocker, and the TRPC channel blockers flufenamic acid, 2-APB and
SKF 96365 inhibited plateau potential and persistent activity, while the TRPV channel blocker
ruthenium red did not have any inhibitory effect. Interestingly, the diacylglycerol analog OAG
which activates TRPC3/6/7 channels failed to induce the plateau potential and persistent firing.
Voltage clamp analysis revealed a current-voltage relationship typical of TRPC4/5-containing
channels with a double-rectifying current that reverses at 0 mV. A specific intracellular peptide
designed to disrupt the interaction between the PDZ binding motif of TRPC4/5 channels and
NHERF/PLCβ was found to be inhibitory. Finally, intracellular application of antibodies directed
against the TRPC5 C-terminal domain also blocked CCh-evoked plateau potential and persistent
activity. Taken together, our data show that receptor-operated TRPC channels are required for
the expression of plateau potentials and persistent activity in layer V principal neurons of rat
MEC.
Disclosures: Z. Zhang , None; A. Reboreda, None; A. Alonso, None; P.A. Barker, None; P.
Seguela, None.