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Protein kinase signalling requirements for metabotropic action of kainate receptors in rat CA1 pyramidal neurones

Protein kinase signalling requirements for metabotropic action of kainate receptors in rat CA1 pyramidal neurones
Protein kinase signalling requirements for metabotropic action of kainate receptors in rat CA1 pyramidal neurones
Hippocampal pyramidal neurons display a Ca2+-dependent K+ current responsible for the slow afterhyperpolarization (IsAHP), a prominent regulator of excitability. There is considerable transmitter convergence onto IsAHP but little information about the interplay between the kinase-based transduction mechanisms underlying transmitter action. We have added to existing information about the role of PKC in kainate receptor actions by demonstrating that direct postsynaptic activation of PKC with either OAG or indolactam is sufficient to inhibit IsAHP. The physiological correlate of this action - activation of PKC by kainate receptors - requires GÑi/o proteins. The cAMP/PKA system is well documented to subserve the actions of monoamine transmitters. We have found an additional role for the cAMP/PKA system as a requirement for kainate receptor-mediated inhibition of IsAHP. Inhibition of adenylyl cyclase with dideoxyadenosine or PKA with either H-89 or RpcAMPs blocked kainate receptor-mediated actions but did not prevent the actions of direct PKC activation with either OAG or indolactam. We therefore propose that the PKA requirement is upstream from the actions of PKC. We additionally report a downstream link in the form of increased MAP kinase activity which may explain the long duration of metabotropic actions of kainate receptors on IsAHP.
Kainate receptor, calcium-activated potassium current, afterhyperpolarization, PKC, PKA, MAP kinase
0022-3751
363-373
Grabauskas, Gintautas
4bea30af-4ebc-41f5-8bae-2833d0261a44
Lancaster, Barrie
f75b7069-70fc-419e-a37e-fc9edbb75ae0
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Wheal, Howard
50ba5833-9920-407a-a48a-1fe917534b74
Grabauskas, Gintautas
4bea30af-4ebc-41f5-8bae-2833d0261a44
Lancaster, Barrie
f75b7069-70fc-419e-a37e-fc9edbb75ae0
O'Connor, Vincent
8021b06c-01a0-4925-9dde-a61c8fe278ca
Wheal, Howard
50ba5833-9920-407a-a48a-1fe917534b74

Grabauskas, Gintautas, Lancaster, Barrie, O'Connor, Vincent and Wheal, Howard (2007) Protein kinase signalling requirements for metabotropic action of kainate receptors in rat CA1 pyramidal neurones. Journal of Physiology, 579 (2), 363-373. (doi:10.1113/jphysiol.2006.122051).

Record type: Article

Abstract

Hippocampal pyramidal neurons display a Ca2+-dependent K+ current responsible for the slow afterhyperpolarization (IsAHP), a prominent regulator of excitability. There is considerable transmitter convergence onto IsAHP but little information about the interplay between the kinase-based transduction mechanisms underlying transmitter action. We have added to existing information about the role of PKC in kainate receptor actions by demonstrating that direct postsynaptic activation of PKC with either OAG or indolactam is sufficient to inhibit IsAHP. The physiological correlate of this action - activation of PKC by kainate receptors - requires GÑi/o proteins. The cAMP/PKA system is well documented to subserve the actions of monoamine transmitters. We have found an additional role for the cAMP/PKA system as a requirement for kainate receptor-mediated inhibition of IsAHP. Inhibition of adenylyl cyclase with dideoxyadenosine or PKA with either H-89 or RpcAMPs blocked kainate receptor-mediated actions but did not prevent the actions of direct PKC activation with either OAG or indolactam. We therefore propose that the PKA requirement is upstream from the actions of PKC. We additionally report a downstream link in the form of increased MAP kinase activity which may explain the long duration of metabotropic actions of kainate receptors on IsAHP.

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Submitted date: 3 October 2006
Published date: 1 March 2007
Keywords: Kainate receptor, calcium-activated potassium current, afterhyperpolarization, PKC, PKA, MAP kinase
Organisations: Biological Sciences

Identifiers

Local EPrints ID: 43742
URI: http://eprints.soton.ac.uk/id/eprint/43742
ISSN: 0022-3751
PURE UUID: 4cd95f17-4150-4900-a81d-6e8b9c8e0130
ORCID for Vincent O'Connor: ORCID iD orcid.org/0000-0003-3185-5709

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Date deposited: 30 Jan 2007
Last modified: 16 Mar 2024 03:13

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Contributors

Author: Gintautas Grabauskas
Author: Barrie Lancaster
Author: Howard Wheal

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