The University of Southampton
University of Southampton Institutional Repository

The mechanism of kainic acid receptor-induced inhibition of I-sAHP in CA1 pyramidal neurones

Melyan, Z., Lancaster, B. and Wheal, H.V. (2001) The mechanism of kainic acid receptor-induced inhibition of I-sAHP in CA1 pyramidal neurones The Journal of Physiology, 536, (174), 27P-27P.

Record type: Article

Abstract

The slow afterhyperpolarisation current (IsAHP) in CA1 pyramidal neurones is reduced in kainic acid-lesioned hippocampus and this effect leads to an increase in cell excitability (Ashwood et al. 1986). We investigated the mechanisms of kainic acid-induced inhibition using whole-cell patch-clamp experiments.
Hippocampal slices were obtained from humanely killed 14- to 21-day-old rats. The recordings were made from CA1 pyramidal cells using KMeSO4-containing pipettes. Voltage steps (60 mV for 80 ms) were applied every 20 s to generate IsAHP.
Bath application of kainic acid produced concentration-dependent inhibition of IsAHP that reached a plateau of 34 % at 100-200 nM (IC50 = 15 nM; n = 7). The inhibition was not accompanied by an inward current and persisted in the presence of 1 µM TTX + 5 mM TEA (n = 8), suggesting postsynaptic localisation of the receptors. The AMPA/KA blocker CNQX (20 µM; n = 6) abolished the action of kainic acid, whereas a selective antagonist of AMPA receptors, GYKI52466 (100 µM), was ineffective (n = 5). The effect of kainate could be reproduced by domoic acid (200 nM; n = 7), but not by the potent agonist of AMPA receptors (S)-5-fluorowillardiine (300 nM; n = 7). The GluR5 kainate receptor agonist ATPA (2 µM; n = 5) did not produce any inhibition. The results are consistent with an action of kainate mediated by GluR6-containing kainate receptors, and imply that a metabotropic function may be involved as reported for presynaptic kainate receptors (Rodriguez-Moreno & Lerma, 1998). This was tested by pre-incubation of the slices with the protein kinase C inhibitor calphostin C (1 µM); this treatment prevented kainate-induced inhibition (n = 10). Subsequent application of noradrenaline (10 µM; n = 4) blocked IsAHP, demonstrating that PKA-dependent inhibition remained intact. In current-clamp experiments, kainic acid (200 nM) did not reduce either the width or the amplitude of calcium spikes recorded following a brief depolarising step (n = 8). This suggests that kainate inhibition of IsAHP was not due to a reduction in Ca2+ influx.
These data indicate that GluR6 kainate receptors on CA1 pyramidal cells not only mediate ionic currents (Bureau et al. 1999) but have metabotropic actions leading to increased cell excitability.This work is supported by The Wellcome Trust.

Full text not available from this repository.

More information

Published date: 1 November 2001
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 56455
URI: http://eprints.soton.ac.uk/id/eprint/56455
ISSN: 0022-3751
PURE UUID: 6c80526f-aa2a-4ca3-8106-39c86056a89d

Catalogue record

Date deposited: 11 Aug 2008
Last modified: 17 Jul 2017 14:30

Export record

Contributors

Author: Z. Melyan
Author: B. Lancaster
Author: H.V. Wheal

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×