title: Protein kinase signalling requirements for metabotropic action of kainate receptors in rat CA1 pyramidal neurones.
abstract: Hippocampal pyramidal neurones display a Ca(2+)-dependent K(+) current responsible for the slow afterhyperpolarization (I(sAHP)), a prominent regulator of excitability. There is considerable transmitter convergence onto I(sAHP) 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 protein kinase C (PKC) in kainate receptor actions by demonstrating that direct postsynaptic activation of PKC with either 1-oleoyl-2-acethylsn-glycerol (OAG) or indolactam is sufficient to inhibit I(sAHP). The physiological correlate of this action - activation of PKC by kainate receptors - requires G alpha(i/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 I(sAHP). Inhibition of adenylyl cyclase with dideoxyadenosine or PKA with either H89 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 mitogen-activated protein (MAP) kinase activity, which may explain the long duration of metabotropic actions of kainate receptors on I(sAHP).
authors.affiliation: School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
authors.forename: Gintautas
authors.initials: G
authors.lastname: Grabauskas
authors.forename: Barrie
authors.initials: B
authors.lastname: Lancaster
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Connor
authors.forename: Howard V
authors.initials: HV
authors.lastname: Wheal
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004075:Diglycerides / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000378:metabolism*; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018092:Kainic Acid Receptors / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D002273:Carcinogens; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D004075:Diglycerides; D019204:GTP-Binding Proteins; D007211:Indoles; D007769:Lactams; D020929:Mitogen-Activated Protein Kinase Kinases; D011493:Protein Kinase C; D018092:Kainic Acid Receptors; C038237:1-oleoyl-2-acetylglycerol; C043969:indolactam V